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Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

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Muizenplagen in Nederland: oorzaken en bestrijding
Apeldoorn, R.C. van - \ 2005
Wageningen : Alterra (Alterra-rapport 1234) - 40
microtus arvalis - arvicola terrestris - apodemus sylvaticus - muizen - plagen - plagen veroorzaakt door gewervelde dieren - plagenbestrijding - nederland - friesland - alblasserwaard - mice - pests - vertebrate pests - pest control - netherlands
In 2005 werd aan grasland in bepaalde delen van Friesland een grote schade geconstateerd, die veroorzaakt is door de veldmuis. De veldmuisplaag en opgetreden schades in Friesland zijn vergeleken met die in de Alblasserwaard in de jaren 1974 en 1980. Naar aanleiding van de hoge dichtheden in Friesland is de cycliciteit in het optreden hiervan (piekjaren) kwalitatief geanalyseerd. De meest recente inzichten in de factoren die piekjaren kunnen veroorzaken, in relatie tot soortspecifieke kenmerken van de veldmuis, worden beschreven. Tevens worden maatregelen en middelen ter bestrijding van plagen vermeld. Hierbij is ook gekeken naar maatregelen in het buitenland, vooral Duitsland. Conclusies worden getrokken en aanbevelingen gedaan om hoge dichtheden van de soort te voorkomen.
Bodemverontreiniging in de Biesbosch en doorvergiftiging naar kleine zoogdieren
Bosveld, A.T.C. ; Bie, P.A.F. de; Hamers, T. - \ 2003
Wageningen : Alterra (Alterra-rapport 654) - 64
bodemverontreiniging - zware metalen - polychloorbifenylen - vergiftiging - sorex araneus - muizen - muridae - fauna - histopathologie - enzymen - nederland - noord-brabant - zuid-holland - biesbosch - soil pollution - heavy metals - polychlorinated biphenyls - poisoning - mice - histopathology - enzymes - netherlands
In de Biesbosch worden bij overstromingen sedimenten afgezet op landbodem. Hiermee komen verontreinigingen zoals PAK's, PCB's en zware metalen beschikbaar voor de terrestrische voedselketen. Onderzocht is in welke concentraties deze verontreinigingen voorkomen in de landbodem en in hoeverre doorvergiftiging optreedt naar kleine zoogdieren. De voornamelijk planten en zaden etende woelmuis en de op bodemfauna (o.a. regenwormen) foeragerende bosspitsmuis zijn onderzocht. Dieren uit regelmatig overstroomde gebieden blijken hogere concentraties verontreinigingen in hun lichaam te hebben en vertonen duidelijke effecten op cytochroom P450 enzymfuncties (o.a. EROD). Daarnaast treden bij deze dieren in sommige gevallen ook effecten op in verschillende organen (lever, nier, gonaden) of op het lichaamsgewicht.
Opnieuw sterfte van jonge bomen door woelmuizen
Moraal, L.G. - \ 2002
Vakblad Natuurbeheer 41 (2002)4. - ISSN 1388-4875 - p. 67 - 69.
bosschade - woelmuizen - bosbomen - dode bomen - knaagdierenbestrijding - preventie - dieren - bomen - bebossing - muizen - schadelijke dieren - bos - ecologie - knaagdieren - woelmuis - zoogdieren - afforestation - forest damage - trees - animals - mice - voles - forest trees - dead trees - rodent control - prevention - noxious animals
In het begin van de jaren negentig trad er behoorlijk veel schade op bij bosaanleg in het kader van de Randstadgroenstructuur en de set-aside regelingen in Groningen en Drenthe. De boompjes waren geplant op voormalige landbouwgrond. Door snelle verruiging van de vegetatie, ontstaat er voor woelmuizen een zeer gunstige biotoop. Vraat van muizen in de winterperiode aan de bast en wortels waardoor de boompjes kunnen afsterven.
Influence of dietary protein sources on putative in vitro and in vivo colon cancer biomarkers
Vis, E.H. - \ 2002
Wageningen University. Promotor(en): J.H. Koeman; Tiny van Boekel. - S.l. : S.n. - ISBN 9789058086525 - 160
voedingseiwit - caseïnaten - sojaeiwit - colorectaal kanker - rattenvoeding - muizen - biologische indicatoren - dietary protein - caseinates - soya protein - colorectal cancer - rat feeding - mice - biological indicators
<p>Colon cancer (cancer of the large intestine) is a worldwide problem in especially Western countries. The diet might be responsible for up to 90% of these colon cancer cases. This means that decreasing colon cancer risk should be possible by changing the diet. The research presented in this thesis concerns the question what the influence is of dietary protein sources on colon cancer risk. As described in <strong>Chapter</strong><strong>1</strong> , casein was compared to other dietary protein sources (mainly soy protein) for its influence on:</p><OL><p><LI>the carcinogen scavenging capacity of proteins,</LI></p><p><LI>early stages of colon cancer,</LI></p><p><LI>fecal colon cancer biomarkers.</LI></p></OL><strong><p>Chapter</strong><strong>2</strong> provides information on various fields of study in the research on dietary proteins and colon cancer, including background information on the methods used. It is explained how dietary proteins can act as carcinogen scavengers by binding to carcinogens in the gastro-intestinal lumen. The carcinogen can be transported along the intestinal tract and be taken up by the body. If a carcinogen is not taken up, it will be excreted with the feces. Furthermore, the influence of the <em>amount</em> of protein intake in the diet on colon cancer risk is discussed. It is concluded that either no or a positive correlation between the amount of protein intake and colon cancer risk, exists. Another important research area is protein digestibility because a low protein digestibility results in a high amount of protein in the colon. Furthermore, the amino acid composition of a protein is important for two reasons. When an essential amino acid is present in a limiting amount, growth of both the individual and the tumor is inhibited. Secondly, some amino acids are needed for specific biological functions. For example, sulfur containing amino acids can stimulate the biotransformational system. The last important factor discussed in the research area of proteins on colon cancer risk is the presence of various non-protein components. As an example, saponins and isoflavones present in many soy proteins and known to be biologically active, are discussed.</p><p>In Chapter 3 and 4 it is described how dietary proteins can scavenge carcinogens <em>in vitro</em> . In <strong>Chapter</strong><strong>3</strong> it is shown that carcinogen scavenging is influenced by many factors, such as heat treatment of the protein, degree of protein digestion and presence of bile acids or lipase. Protein type did not have a major influence so no effect of feeding different dietary protein sources on colon cancer risk is expected.</p><p>In <strong>Chapter</strong><strong>4</strong> it is shown that the carcinogen scavenging capacity of proteins is also very much dependent on the type of carcinogen. Benzo[a]pyrene, a large non-reactive pro-carcinogen, interacted only with intact dietary proteins, whereas MNNG, as described in Chapter 3, strongly interacted with both intact as well as hydrolyzed proteins. Again no difference between dietary protein sources was shown, suggesting no difference in colon cancer risk.</p><p>In <strong>Chapter 5</strong> the first animal experiments are described. In Study 1, the influence of the addition of 1% methionine to the diet on colonic cell proliferation was tested. Methionine is an important methyl donor in many metabolic routes and is present in different amounts in casein and soy protein preparations. Colonic cell proliferation was used as an indication of colon cancer risk, because cell proliferation is an important phase in the process of colon cancer. The study showed no influence of methionine on colonic cell proliferation. In Study 2 rats were fed different amounts of soy non-nutrients to test the influence of these non-nutrients on several parameters in the feces. Most important fecal parameter was the fecal fat percentage, because earlier studies reported a correlation between high fecal fat and colon tumors. Study 2 showed that fecal fat excretion in rats is dependent on the amount of soy non-nutrients in the diet. However, the difference in fecal fat excretion between casein and soy protein was smaller (factor 2) than reported in literature. Therefore no major effect on colon cancer risk is expected. The influence of soy non-nutrients on processes in the colon was shown in Study 3. In this <em>in vitro</em> study, soy non-nutrients strongly reduced bile acid induced cell damage, suggesting a small protective effect of dietary soy protein.</p><p>In <strong>Chapter 6</strong> two animal studies on the influence of casein and soy protein on colonic cell proliferation are described. The studies showed no difference in colonic cell proliferation between these two protein sources. However different results for the casein and soy protein diets were obtained for several parameters that were measured in the feces of the animals. These fecal parameters were measured because they show how important steps in the process of colon cancer development are affected. A high fecal fat percentage correlates with a high number of tumors in the colon. Fecal alkaline phosphatase (ALP) activity represents damage to cells of the colonic epithelium because epithelial cells exhibited a high ALP activity. Bile acids and free fatty acids can damage the colonic epithelium because of their lytic potential. The cytolytic activity measures this damaging capacity, because it measures the lytic potential of the colonic contents towards cells in an <em>in vitro</em> test. The pH of the fecal contents was measured because a low pH represents a healthy colonic environment. Fecal<FONT FACE="Symbol">b</font>-glucuronidase and<FONT FACE="Symbol">b</font>-glucosidase activities were measured because they represent the capacity of the colonic contents to liberate toxicants in the colonic lumen that were earlier detoxified by the liver.</p><p>Results on cytolytic activity confirmed the lack of difference between casein and soy on colonic cell proliferation because there was no difference between diets. Fecal fat excretion was doubled after feeding soy protein compared to casein. After feeding soy protein, fecal water bile acid concentrations and ALP activity were decreased. However,<FONT FACE="Symbol">b</font>-glucuronidase and<FONT FACE="Symbol">b</font>-glucosidase were increased 10-100 fold. Overall, no consistent conclusion on fecal parameters was possible.</p><p>In <strong>Chapter 7</strong> the influence of casein, soy protein isolate and soy flour on colonic aberrant crypt foci (ACF) is tested. ACFs are considered to be early stages of colonic tumors. Overall no consistent difference of casein and soy protein on aberrant crypt foci was detected. Again<FONT FACE="Symbol">b</font>-glucuronidase,<FONT FACE="Symbol">b</font>-glucosidase and ALP activities were measured in feces.<FONT FACE="Symbol">b</font>-Glucuronidase and<FONT FACE="Symbol">b</font>-glucosidase activities were significantly increased after feeding soy protein suggesting an increased risk after soy feeding.</p><p>In <strong>Chapter 8</strong> the influence of casein, soy protein isolate, soy protein flour and red meat is tested on the occurrence of intestinal polyps in the <em>Apc <sup>Min</em></SUP>model. In this model, mice with a defect <em>Apc</em> gene spontaneously develop polyps in both small and large intestine. The four diets showed no difference in the occurrence of polyps. Again several differences were observed in the fecal parameters.<FONT FACE="Symbol">b</font>-Glucuronidase and<FONT FACE="Symbol">b</font>-glucosidase were strongly increased after soy protein compared to the other diets. The pH of the colonic contents was decreased after soy flour feeding indicating fermentation of fibers present in soy flour preparations has a major influence. Furthermore it was shown that heme in the form of meat protein is not nearly as lytic as heme added to the diet in the pure form. No differences between the diets were found for free fatty acids. The concentrations of bile acids in fecal water were decreased for especially the soy protein diets. Overall, fecal parameters showed marked differences, but again no consistent protective or risk inducing effects.</p><p>In <strong>Chapter 9</strong> all studies performed are compared and discussed with an emphasis on the animal studies. Overall, fecal fat excretion was consistently doubled after feeding soy protein.<FONT FACE="Symbol">b</font>-Glucuronidase and<FONT FACE="Symbol">b</font>-glucosidase, able to release toxicants, were consistently increased after feeding soy protein. Bile acids in fecal water, able to damage colonic epithelium, were consistently decreased after soy protein feeding. Other fecal parameters either showed no difference between diets (pH, cytolytic activity) or variable results (ALP, free fatty acids). It was shown that fecal magnesium excretion has no predictive value for colonic cell proliferation. Fecal<FONT FACE="Symbol">b</font>-glucuronidase,<FONT FACE="Symbol">b</font>-glucosidase, ALP, bile acids and free fatty acids showed large differences in absolute values between animal experiments. Possibly the effect caused by some protein sources on fecal parameters, is also partly dependent on interaction with other dietary constituents such as fat and fiber or non-protein components. Because no differences on cell proliferation, aberrant crypt foci and intestinal polyps were found, a difference in colon cancer risk after consumption of casein or soy protein is unlikely. Correlation studies revealed that none of the fecal parameters tested consistently predicted the outcome of the colonic parameters tested, stressing the need for further research in this area. Because of the variable composition and results obtained with soy, it was concluded that one should be very cautious concerning the interpretation of studies in which soy protein preparations are used.</p><p>The main conclusion from the studies performed is that many significant differences occurred between casein and other dietary protein sources such as soy. Differences specifially occurred on parameters related to the carcinogen scavenging capacity of proteins and on fecal parameters such as fecal bile acid, ALP and<FONT FACE="Symbol">b</font>-glucuronidase excretion. However, no consistent <em>in vivo</em> protective effect of casein occurred on colon cancer, based on markers as colonic cell proliferation, aberrant crypt foci formation and polyp formation. Therefore results do not support an advice on consuming either more or less casein or soy protein containing products.
Psychoneuroimmunology in pigs can the immune system cope with intensive husbandry conditions
Groot, J. de - \ 2001
- 141
varkens - muizen - immuunsysteem - immuniteit - immunologie - intensieve dierhouderij - stress - zenuwstelsel - dierziekten - beschadigingen - adaptatie - psychologische fysiologie - pigs - mice - immune system - immunity - immunology - intensive husbandry - nervous system - animal diseases - injuries - adaptation - psychological physiology
Kleine zoogdieren betrouwbaarder en efficiënter inventariseren
Bergers, P.J.M. ; Haye, M. La - \ 2000
De Levende Natuur 101 (2000)2. - ISSN 0024-1520 - p. 52 - 58.
kleine zoogdieren - muizen - inventarisaties - karteringen - vallen - vangmethoden - veldwerk - small mammals - mice - inventories - surveys - traps - trapping - field work
Een vergelijking van de resultaten van drie inventarisatiemethoden om de aanwezigheid van kleine zoogdieren in een gebied vast te stellen: standaardmethode met Longworth inloopvallen en zes controles; IBN-methode, idem met vier controles; IBN+-methode, idem maar vallen overdag dicht
Om het behoud van de noordse woelmuis? Feiten en veronderstellingen
Apeldoorn, R.C. van - \ 2000
Zoogdier 11 (2000)2. - ISSN 0925-1006 - p. 24 - 28.
microtus oeconomus - muridae - muizen - bedreigde soorten - bescherming - conservering - habitats - territorium - milieu - populatie-ecologie - dierecologie - concurrentie tussen dieren - dieren - introductie - geïntroduceerde soorten - vrijgeven - genetische variatie - genetische diversiteit - genetische erosie - mice - endangered species - protection - conservation - territory - environment - population ecology - animal ecology - animal competition - animals - introduction - introduced species - release - genetic variation - genetic diversity - genetic erosion
Het belang van verschillende factoren die een rol spelen bij het behoud van de noordse woelmuis (Microtus oeconomus) in Nederland: habitatfragmentatie (versnippering); concurrentie met andere woelmuizen; genetische variatie en verarming (lokaal en regionaal). Aan de voorwaarden voor herintroductie is niet voldaan en er is meer onderzoek nodig
Muizen als zaadsjouwers en grasmaaiers
Smit, R. ; Ouden, J. den - \ 2000
Zoogdier 11 (2000)3. - ISSN 0925-1006 - p. 3 - 6.
apodemus sylvaticus - microtus agrestis - clethrionomys glareolus - microtus arvalis - muizen - habitats - milieu - vegetatie - bossen - zaadpredatie - zaadverspreiding - zaden - verjonging - kieming - dierecologie - voedingsgedrag - voedingsgewoonten - bosecologie - mice - environment - vegetation - forests - seed predation - seed dispersal - seeds - regeneration - germination - animal ecology - feeding behaviour - feeding habits - forest ecology
De invloed van muizen op de vegetatie, en het verband tussen de vegetatiestructuur en het voorkomen van de verschillende soorten muizen (bosmuis, rosse woelmuis, aardmuis, veldmuis; spitsmuizen buiten beschouwing gelaten). Resultaten van onderzoek in heiden en bossen op arme zandgronden van de Veluwe naar muizenbestand en zaadpredatie en zaadverspreiding. Muizen kunnen een enorm effect op de kieming van bomen hebben
Dark-bellied Brent Geese Branta bernicla bernicla forego breeding when Arctic Foxes Alopex lagopus are present during nest initiation
Spaans, B. ; Blijleven, H.J. ; Popov, I.U. ; Rykhlikova, M.E. ; Ebbinge, B.S. - \ 1998
Ardea 86 (1998)1. - ISSN 0373-2266 - p. 11 - 20.
nesten - anser - ganzen - predatie - canidae - muridae - muizen - ratten - aziatisch rusland - stroomgebieden - nests - geese - predation - mice - rats - russian far east - watersheds
In an area north of the Pyasina delta in Taimyr (Russia), nest distribution, nest initiation and breeding success of Brent Geese Branta bernicla bernicla were studied in six successive summer seasons from 1990-1995 in relation to lemming and Arctic Fox Alopex lagopus abundance. Lemming abundance conformed to the well-known three-year cycle with peaks in 1991 and 1994. Wandering Arctic Foxes were numerous in 1992, one of the two years following a lemming peak. This was the only year in which foxes visited the small offshore island where Brent Geese used to nest. Although Brent Geese arrived in time that year, the majority did not even start to breed and disappeared. Thus the actual mechanism causing failure in 1992 was disturbance rather than predation and Brent Geese appeared to be able to forego breeding at the very last moment. In the unexpected absence of foxes in the second predator year 1995, Brent Geese incubated successfully on the small islands in our study area. However, they failed to raise their goslings as these were all predated, not by foxes but probably by gulls.
De noordse woelmuis
Bergers, P.J.M. - \ 1998
De Levende Natuur 99 (1998)6. - ISSN 0024-1520 - p. 222 - 223.
microtus oeconomus - muizen - habitats - nederland - mice - netherlands
Non-homologous chromosome synapsis during mouse meiosis : consequences for male fertility and survival of progeny
Peters, A.H.F.M. - \ 1997
Agricultural University. Promotor(en): C. Heyting; P. de Boer. - S.l. : Peters - ISBN 9789054857761 - 182
muridae - muizen - meiose - geslachtelijke voortplanting - parthenogenese - polyembryologie - vruchtbaarheid - overleving - levensvatbaarheid - interacties - milieu - uitsterven - stofverplaatsing - chromosoomtranslocatie - chromosomen - cytologie - histologie - mice - meiosis - sexual reproduction - parthenogenesis - polyembryony - fertility - survival - viability - interactions - environment - extinction - translocation - chromosome translocation - chromosomes - cytology - histology
In the mouse, heterozygosity for several reciprocal and Robertsonian translocations is associated with impairment of chromosome synapsis and suppression of crossover formation in segments near the points of exchange during prophase of meiosis. This thesis describes the analysis of the consequences of the occurrence of non-homologous synapsis and/or suppression of meiotic crossover formation over many successive generations for male fertility and viability of the progeny.<p>For studying chromosome synapsis, we modified a drying down technique which results in high yields of nuclei of all first meiotic prophase stages in both male and female from only small amounts of tissue (chapter 2). Preparations are suitable for synaptonemal complex (SC) analysis by normal light and electron microscopy (chapters 2, 3 and 7), for fluorescence immunocytochemistry and <em>in situ</em> hybridization (chapters 2, 8).<p>In the study presented in <em>chapter 3,</em> we analysed the variation in male fertility of mice double heterozygous for two near identical reciprocal translocations T(1;13)70H and T(1;13)1Wa in relation to the synaptic behaviour of two differently sized heteromorphic bivalents during meiotic prophase. Male fertility rises when non-homologous synapsis in the small 1 <sup>13</SUP>heteromorphic bivalent, leading to a "symmetrical" SC, is more frequent at the initial prophase stages. Based on the data presented, we favour the "unsaturated pairing site" model as the primary cause for male sterility.<p>In T70H/T1Wa females not all heterologous synapsis within the small heteromorphic bivalent is effectuated during the early stages of meiosis; some is achieved lateron by the mechanism of "synaptic adjustment" (chapter 3). Each heteromorphic bivalent contains a copy of the chromosome 1 region between the T70H and T1Wa breakpoints which is about 10 cM in size (Δ1 segment). Although axial elements representing these Δ1 segments are seen to approach each other during early meiotic prophase stages, they never successfully constitute a synaptonemal complex in either sex (chapter 3). This agrees with the fact that in earlier cytogenetic studies quadrivalents were never seen at both male and female diakinesismetaphase 1.<p>In <em>chapter 7,</em> we demonstrate that male fertility of the T70H/T1Wa mice is not only determined by the chromosomal constitution of the carrier but is additionally influenced by the pairing or synaptic history in previous meioses of especially the T70H and T1Wa short translocation chromosomes. Fertility of T70H/T1Wa males is more impaired after one or more successive transmissions of the T1Wa translocation chromosomes through a heteromorphic bivalent configuration, irrespective of the sex of the transmitting parent.<p>Furthermore, we show that the introduction of the Robertsonian translocation Rb(l1.13)4Bnr into the T70H/T1Wa karyotype restores fertility of double heterozygous males by stimulating non-homologous synapsis of the small heteromorphic bivalent. We speculate that this Rb4Bnr effect is mediated by a prolongation of the early stages of meiotic prophase I.<p>Successive female transmissions of the T1Wa translocation chromosomes in the presence of Rb4Bnr inititially resulted in an increase of the capacity for early meiotic nonhomologous synapsis within the small heteromorphic bivalent, leading to a restoration of fertility for the majority of carriers. Subsequently, a decrease of the capacity of the small heteromorphic bivalent to fully synapse was noticed, although a higher than original (F1) background level of male fertility remained.<p>These variations in male fertility are most likely based on epigenetic variance, reflected as the capacity to engage into non-homologous synapsis early in male meiosis leading to a "symmetrical" SC, despite the different amounts of chromatin to accommodate.<p>In <em>chapter 4,</em> the localization of several microsatellite markers and single copy genes relative to the T70H and T1Wa breakpoints, using quantitative PCR, quantitative Southern blotting and <em>in situ</em> hybridization, is described.<p>In <em>chapter 5,</em> we investigated the level of suppression of meiotic recombination and impairment of chromosome synapsis in T70H heterozygotes in relation to the viability of the progeny. For T70H/+ females, the introgression of the D1Mit4, D1Mit20 and D1Mit122 microsatellite marker alleles positioned distal of the T70H breakpoint on the normal chromosome 1 into the 13 <sup>1</SUP>T70H long translocation chromosome was suppressed in a distance dependent manner. This effect was more pronounced in T70H/+ females, additionally homozygous for Rb4Bnr. The delay in introgression was paralleled by a reduction of the frequency and extent of non-homologous synapsis in segments near the T70H breakpoints of the pachytene translocation multivalents in T70H/+ and Rb4BnT70H/Rb4Bnr+ males. The extend of non-homologous synapsis around the centre of the synaptic cross configuration in these males correlated with fluctuations in prenatal viability of segregating translocation homozygotes in crosses between (Rb4Bnr)T70H homozygous males and heterozygous females when meiotic drive at the female second meiotic division is excluded. The reduction in viability is explained by the gain of mutations resulting from incorrect processing of recombination intermediates which is due to non-homologous synapsis around the translocation breakpoints.<p>In <em>chapter</em> 6, we analysed the consequences of the absence of crossing over for regions between the T70H and T1Wa breakpoints (Δ1 and Δ13 segments) of the Rb4BnrT1Wa translocation chromosomes, which have been transmitted for over 20 generations via heteromorphic bivalents in Rb4BnrT70H/Rb4BnrT1Wa females. Survival of heterozygous and homozygous carriers for these segments was taken as the phenotypic endpoint. The viability of progeny of crosses between Rb4BnrT70H homozygous males and Rb4BnrT70H/Rb4BnrT1Wa females, of which the latter principally produce 4 types of gametes, was estimated using a haplotype analysis of microsatellites in the Δ1 segment for genotyping (see chapter 4). We observed no differences in the pre- and postnatal survival rates of the double heterozygous and 13 <sup>1</SUP>H, 13 <sup>1</SUP>H, 1 <sup>13</SUP>Wa 1 <sup>13</SUP>H "duplication" progeny in which the Δ1 and Δ13 segments of the T1Wa translocation chromosomes had either no, an onegeneration or a multi-generation history of non-homologous synapsis in heteromorphic bivalents during previous female meioses. In addition, intercrossing of Rb4BnrT70H/Rb4BnrT1Wa double heterozygotes after genetic isolation of these Δ1 and Δ13 segments for 20 to 22 generations, showed that the viability of the Rb4BnrT1Wa homozygotes was not different from the Rb4BnrT70H homozygous and Rb4BnrT70H/Rb4BnrT1Wa karyotypes generated by this cross. Thus, exclusion of the Δ1 and Δ13 segments from meiotic crossing over within non-homologous synapsed heteromorphic bivalents during 20 to 25 successive generations does not result in an accumulation of recessive lethal mutations or an increased susceptibility for gaining dominant lethal mutations.<p>For the D1Mit122 microsatellite used in offspring haplotyping a higher mutation frequency was observed after transmission through a double heterozygous than after transmission through a T70H homozygous karyotype (chapter 6). On the basis of the identity of the mutations, the ectopic pairing of the St2 gene copies (containing D1Mit122) during meiosis of T70H/T1Wa males (chapter 8) and the observation of ectopic homologous contacts of the Δ1 segments during the zygotene stage without SC formation (chapter 3), we speculate that these mutations are the result of ectopic homologous gene conversion events most likely occurring in the absence of a synaptonemal complex.<p>The crossover suppressive influence of the Rb translocation on the Δ1 segment (chapter 5) enabled us to analyze the effects of introgression of genetic material from the Swiss +/+ stock into the translocation karyotypes. Introgression of "new" genetic material correlated with an increase in littersize of Rb4BnrT70H homozygotes (chapter 5), an improvement of the life expectancy of Δ1 duplication offspring from double heterozygous mothers (chapter 6) and a clear improvement of male fertility in double heterozygous and T70H homozygous males also carrying Rb4Bnr (chapter 7). These pleiotrophic findings are discussed in chapter 8 in terms of genetic versus epigenetic mechanisms of inheritance.<p>Finally, when T1Wa was backcrossed for many generations to the Rb4BnrT70H/Rb4BnrT70H karyotype, essentially precluding genetic recombination in the Δ1 and Δ13 segments, or when T1Wa was combined with Rb4Bnr after many successive transmissions via alternating T1Wa heterozygotes and homozygotes, stable Rb4BnrT1Wa homozygous lines could not be bred (chapter 8). Especially female reproductive performance decreases after repeated male and female homologous meiosis. As non-homologous synapsis in the centre of the synaptic cross configuration in T1Wa/+ males is common too (unpublished results), more work into the genetic stability of chromosome segments, that have a history of hindered homologous interaction, is indicated (chapter 8).
Changing gap junctional intercellular communication in mouse epidermal cells during tumorigenesis : a study on underlying processes
Jansen, L.A.M. - \ 1996
Agricultural University. Promotor(en): J.H. Koeman; W.M.F. Jongen; G.J. de Vrije. - S.l. : S.n. - ISBN 9789054855798 - 128
neoplasma's - muridae - muizen - signaaltransductie - oncologie - celinteracties - neoplasms - mice - signal transduction - oncology - cell interactions
Gap junctional intercellular communication (GJIQ plays an important role in the differentiation and growth of cells. Increasing evidence also suggests a role for inhibition of GJIC in the promotion phase of tumor formation. How the level of GJIC is regulated in normal cells, and if this regulation is changed during the process of tumor formation is however not clearly known yet.<p>In the chapters 3 and 4 the studies on the regulation of GJIC by (extracellular and intracellular) Ca <sup><font size="-2">2+</font></SUP>- and cAMP-dependent processes are described for a cell line consisting of initiated cells (3PC), and a carcinoma derived cell line (CA3/7). From these studies it can be concluded that differences exists between the regulation of GJIC in cells representing different stages in the process of tumor formation, and that the short-term regulation of GJIC by intracellular Ca <sup><font size="-2">2+</font></SUP>(Ca<font size="-2"><sup>2+</SUP><sub>i</sub></font>) or by cAMP are different routes of regulation. Furthermore it can be concluded that the presence of cell adhesion molecule E-cadherin on the plasma membrane is a prerequested for a high GJIC level, but that E-cadherin is not involved in the short term regulation of GJIC by Ca<font size="-2"><sup>2+</SUP><sub>i</sub></font>or cAMP.<p>The observed differences between 3PC cells and CA3/7 cells in the regulation of GJIC by intracellular signals suggest that during the process of tumor formation changes have occured in the Ca<font size="-2"><sup>2+</SUP><sub>i</sub></font>- or calmodulin-dependent regulation of GJIC. These differences may be the result of differences in intracellular concentrations of regulating molecules (such as Ca<font size="-2"><sup>2+</SUP><sub>i</sub></font>or CaM) or differences in the sensitivity of enzymes which are dependent of Ca<font size="-2"><sup>2+</SUP><sub>i</sub></font>or CaM. These differences could result in a blocked intercellular communication between cell types representing different stages of tumor formation. For instance, if normal cells with a high GJIC level would come in contact with preneoplastic cells with different intracellular concentrations of calcium, a diffusion of calcium would appear at the moment intercellular gap junctions become functional between the two cell types. This diffusion of calcium will then lead to changed concentrations in the intracellular gap junction regions, which could result in mechanisms closing the gap junction to preserve the cellular homeostasis. Together this might lead to a quickly blocked GJIC between the normal and the preneoplastic cells, which could have a high homoloques GJIC level, as was shown between transformed and non-transformed Balb/c 3T3 cells.<p>Agents which decrease the level of GJIC (including tumor promoters) can play a role in the promotion phase of the process of tumor formation. Several test systems (based on the inhibition of GJIQ for the detection of agents with GJIC inhibiting capacity exist. In these assays however, the target cells for tumor promoters in the process of tumor formation (i.e. initiated cells) are not used. From the work presented in chapter 5 it can be concluded that a cell line consisting of initiated mouse epidermal cells (3PC) is a good model to detect agents with GJIC-inhibiting capacity, and that these cells are more sensitive for inhibition of GJIC compared to carcinomaderived cells. The sensitivity of primary keratinocytes compared to 3PC cells was varying and dependent on the agent used.<p>To determine if the differences between the cell types used for the detection of inhibition of GJIC (chapter 5) are attributable to differences in mechanisms which are thought to play a role in the regulation of GJIC (i.e. connexin amount, connexin phosphorylation, connexin location in the cell, E-cadherin amount, and E-cadherin location in the cell), we studied the effects of tumor promoters on these parameters in the different cell types (chapters 6 and 7). Because calcium plays a role in the regulation of GJIC (chapter 3), we also studied the effect of tumor promoters on Ca<font size="-2"><sup>2+</SUP><sub>i</sub></font>and the role of Ca<font size="-2"><sup>2+</SUP><sub>e</sub></font>on these effects (chapter 8). From these studies, the following conclusions can be drawn: 1) The mechanisms involved in the inhibition of GJIC by tumor promoters are agent- and cell type-dependent; 2) The observed differences in the susceptibility of cells for the inhibition of GJIC by tumor promoters can not be associated with effects of the studied agents on one of the studied parameters; and 3) tumor promoters can change [Ca <sup><font size="-2">2+</font></SUP>] <sub><font size="-2">i</font></sub> , but these changes are not associated with inhibition of GJIC.<p>In addition to the results of the studies on the regulation of GJIC (chapters 3 and 4), the studies with tumor promoters showed that, in the mouse epidermal cells used in these studies, only a decreased immunostaining of Cx43 on the plasma membranes of cells can be related to a decreased GJIC level. However, it must be noted that specific amino acid analysis of Cx43 could finally demonstrate if a relationship between inhibition of GJIC and Cx43 phosphorylation exists et all.<p>The mechanisms regulating the transport of connexins to and from the membrane, as well as the mechanisms involved in the formation of connexons are yet unknown. Because several tumor promoters inhibited GJIC in addition to delocation of both Cx43 and E-cadherin, it should be interesting to study the mechanisms involved in the assembly of gap junction proteins or cell adhesion molecules in the plasma membrane. Such study could lead to a better understanding of the mechanisms involved in (chemical-induced) inhibition of GJIC. A study on the time-related changes in tumor promoter-induced Cx43 inummostaining and E-cadherin immunostaining could give more insight in the role of E-cadherin in the regulation of GJIC. For such a study, also cells transfected with E-cadherin or a connexin could be used.
Zomernesten van de hazelmuis in Zuid-Limburg; ecologie en verspreiding
Foppen, R. ; Verheggen, L. ; Erkenbosch, H. - \ 1995
Natuurhistorisch Maandblad 84 (1995)8. - ISSN 0028-1107 - p. 200 - 212.
dieren - milieu - habitats - muizen - muridae - ratten - territorium - zuid-limburg - animals - environment - mice - rats - territory
Gebiedsgericht en soortgericht beleid in moerassen; de noordse woelmuis als toets
Bergers, P.J.M. ; Apeldoorn, R.C. van - \ 1995
Wageningen : IBN-DLO - 40
bescherming - dieren - uitsterven - bedreigde soorten - conservering - natuurbescherming - recht - wetgeving - beleid - bedrijfsvoering - muridae - muizen - zwampen - moerassen - wetlands - nederland - microtus oeconomus - protection - animals - extinction - endangered species - conservation - nature conservation - law - legislation - policy - management - mice - swamps - marshes - netherlands
Eerste vondst van de rosse woelmuis Clethrionomys glareolus op Schouwen-Duiveland
Bergers, P.J.M. ; Bussink, H. - \ 1995
Lutra 38 (1995). - ISSN 0024-7634 - p. 60 - 61.
dieren - invasie - muizen - migratie - mortaliteit - muridae - populatiedichtheid - populatie-ecologie - populatiegroei - ratten - clethrionomys glareolus - zeeland - animals - invasion - mice - migration - mortality - population density - population ecology - population growth - rats
Effects of vitamin A and [beta]-carotene on respiratory tract carcinogenesis in hamsters : in vivo and in vitro studies
Wolterbeek, A.P.M. - \ 1995
Agricultural University. Promotor(en): J.H. Koeman; V.J. Feron; A.A.J.J.L. Rutten. - S.l. : Wolterbeek - ISBN 9789054853749 - 158
carcinoom - neoplasma's - ademhalingsziekten - retinol - carotenen - provitaminen - carotenoïden - muridae - muizen - ratten - carcinoma - neoplasms - respiratory diseases - carotenes - provitamins - carotenoids - mice - rats
<strong>Summary</strong><br/>Respiratory tract cancer is the leading cause of death by cancer in 'Western' countries. The greater part of lung cancers are caused by smoking. Furthermore, environmental air pollution and occupational exposure contribute to the high incidence of lung cancer. Because it seems to be an almost impossible task to eliminate exposure of man to all these factors, considerable effort has been focused on identifying naturally occurring or synthetic compounds which can prevent the formation of respiratory tract cancer. In this regard, (pro)vitamin A (vitamin A and β-carotene) have been shown very promising. In a large number of epidemiological and experimental studies it has been shown that (pro)vitamin A inhibits the formation of respiratory tract cancer. However, the results of these studies are not always consistent and some studies even showed that (pro)vitamin A increases the incidence of lung cancer. Although the effect of (pro)vitamin A on the formation of respiratory tract cancer has been studied extensively, the mechanisms by which (pro)vitamin A influences the process of respiratory tract carcinogenesis are still not fully understood. In the studies described in this thesis, using both an <em>in vitro</em> and an <em>in</em> vivo approach, the effects of vitamin A and β-carotene on various stages of the process of chemically-induced respiratory tract carcinogenesis were investigated (Figure 1). The emphasis was on the effects of vitamin A and β-carotene on benzo[a]pyrene (B[a]P)-induced DNA-adduct formation, DNA-repair activities, cell proliferation and histomorphological changes in the hamster respiratory tract epithelium. Furthermore, the relationships between DNA-adduct formation, DNA-repair activities, cell proliferation and the expression of the tumour suppressor gene p53 were investigated.<br/> <br/><img src="/wda/abstracts/i1924_1.gif" height="830" width="600"/><br/><em>In vitro studies</em><br/>In the first <em>in vitro</em> experiments, the formation and repair of B[a]P-DNA adducts in hamster and rat tracheal epithelial cells was studied (Chapters 3 and 4). It was shown that <em>in vitro</em> the main DNA adduct formed in hamster tracheal epithelial cells was the trans-addition product of deoxyguanosine and (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-dG). This is the same DNA adduct as formed <em>in vivo</em> in tracheal epithelial cells of hamsters intratracheally treated with B[a]P. Furthermore, it is the same adduct as has been frequently observed in human respiratory tract cells. In rat tracheal epithelial cells two major DNA adducts were found <em>in vitro</em> : the BPDE-dG adduct and an adduct that is probably derived from interaction of <em>syn</em> -BPDE and deoxyadeno- s-ine. Both the formation of B[a]P-DNA adducts and the B[a]P-induced DNA-repair activities in hamster tracheal epithelial cells were time- and concentration-dependent. In rat tracheal epithelial cells, the formation of B[a]P-DNA adducts was 10 times lower than in hamster tracheas. Furthermore, unlike in hamster tracheal epithelial cells, B[a]P did not induce DNA-repair activities in rat tracheal epithelial cells. In the studies described in Chapter 5, the effect of vitamin A and β-carotene on the formation and repair of B[a]P-DNA adducts in hamster tracheal epithelial cells was investigated. It was shown that both vitamin A and β-carotene slightly inhibited the formation of B[a]P-DNA adducts. In addition, vitamin A and β-carotene increased B[a]P-induced DNA-repair activities. This suggests that the observed decrease in B[a]P-DNA adducts is a positive effect of vitamin A and β-carotene, probably also partly caused by an increase in DNA-repair activities. The effect of vitamin A on DNA-adduct formation and DNA-repair activities depended on the concentration of B[a]P versus the concentration of vitamin A. At a low B[a]P concentration relative to the concentration of vitamin A the formation of B[a]P-DNA adducts was inhibited by vitamin A, whereas at a relatively high concentration of B[a]P the formation of DNA adducts was enhanced by vitamin A.<p>The role of B[a]P and vitamin A in cell proliferation in hamster tracheal epithelium in organ culture is described in Chapter 6. It was shown that the effects of B[a]P and vitamin A on cell proliferation strongly depended on the culture medium used; in tracheas cultured in Ham's F12 medium cell proliferation was decreased by B[a]P treatment compared to control tracheas, while cell proliferation in tracheas treated with vitamin A in combination with B[a]P was increased compared to tracheas treated with B[a]P alone. In tracheas cultured in CMRL-1066 medium, the effects of B[a]P and vitamin A on cell proliferation were opposite to those observed in tracheas cultured in Ham's F12 medium: cell proliferation in tracheas cultured in CMRL-1066 medium and treated with B[a]P was increased compared to control tracheas, while vitamin A decreased B[a]P-induced cell proliferation. To explain these opposite effects of B[a]P and vitamin A on cell proliferation, various medium components and growth factors were investigated. The concentration of CaCl <sub><font size="-2">2</font></sub><strong>.</strong> 2H <sub><font size="-2">2</font></sub> O revealed to be the most important factor: supplementation of CaCl <sub><font size="-2">2</font></sub><strong>.</strong> 2H <sub><font size="-2">2</font></sub> O to the Ham's F12 culture medium mimicted the effects of B[a]P and vitamin A on cell proliferation in CMRL-1066 medium. These results clearly indicate that Ca <sup><font size="-2">2+</font></SUP>is an important regulator of proliferation of hamster tracheal epithelial cells. Furthermore, the results of these experiments showed that the level of B[a]P-DNA adducts was inversely related to cell proliferation in tracheas cultured in Ham's F12 medium. Although these results suggest that the tumour suppressor gene p53 might be involved by inhibiting cell proliferation as a consequence of DNA damage, we were unable to show a direct relationship between the level of B[a]P-DNA adducts, cell proliferation and expression of the p53 tumour suppressor protein in hamster tracheal epithelium in organ culture. <em></em><p><em>In vivo studies</em><br/>The most widely applied <em>in vivo</em> model to study the aetiology and pathogenesis of respiratory tract cancer in experimental animals is based on repeated intratracheal instillations of a saline suspension of fine crystalline B[a]P particles attached to ferric oxide as a carrier. Various aspects of this method are discussed in Chapter 2, showing that the dose of B[a]P and the size of the B[a]P particles are the most important variables influencing the tumour response. In a first <em>in vivo</em> experiment into the effect of vitamin A and β-carotene on B[a]P-induced (pre)neoplastic changes in the respiratory tract of hamsters, the response of the respiratory tract epithelium was too low. This might be due to an insuficiently high B[a]P dose, possibly in combination with a relatively insensitive strain of hamsters used. The low response hampered studying potential effects of vitamin A or P-carotene on the (pre)neoplastic response (Chapter 7). An interesting observation in this experiment was an exceptionally low mortality of hamsters fed a high-β-carotene diet. Although we were unable to establish the exact cause of death of hamsters not receiving β-carotene, the most conspicuous difference between hamsters in the high-β-carotene group and hamsters in other groups was a decrease in lipid peroxidation in the livers of hamsters in the former group. Probably, this effect was not only due to the high concentration of β-carotene in the diet, but was also related to a high dietary level of α-tocopherol and ascorbyl palmitate (also present in the β-carotene beads and used to protect β-carotene from oxidation). To obtain a higher tumour response, hamsters were treated in a second experiment with a higher total dose of B[a]P (Chapter 8 and 9). In this study, a clear relationship appeared to exist between the extent of B[a]P-DNA adduct formation, the induction of cell proliferation and the immunocytochemically detected expression of the p53 protein in hamster tracheal epithelial cells. However, in this experiment the formation of B[a]P-DNA adducts was not found to be affected by a high dietary level of β-carotene, probably due to the high B[a]P dose. Furthermore, β-carotene did not affect B[a]P-induced cell proliferation and expression of the p53 protein in tracheal epithelial cells. Chapter 9 describes the histomorphological aspects of this hamster study, using conventional histopathology and immunohistochemical techniques for the detection of various cytokeratins and glutathione <em>S</em> -transferase (GST)-isoenzyme Pi. From this study, it appeared that B[a]P influenced both the expression of cytokeratins and the expression of the GST-isoenzym Pi. However, in accordance with the results described in Chapter 8, β-carotene did not inhibit B[a]P-induced lesions in the respiratory tract epithelium of hamsters.<p><strong>Concluding remarks</strong><br/>Finally, the studies described in this thesis allow the following conclusions:<p>- In vitro, vitamin A and β-carotene decrease slightly but consistently the formation of B[a]P-DNA adducts, probably due to an increase in DNA-repair activities. The effect of vitamin A on the formation of B[a]P-DNA adducts depends on the concentration of B[a]P versus the concentration of vitamin A.<p>- The effects of vitamin A and B[a]P on cell proliferation in hamster tracheal epithelial cells in organ culture strongly depend on the tissue-culture medium used, in particular on the concentration of Ca <sup><font size="-2">2+</font></SUP>in the medium. The effects of B[a]P and vitamin A on cell proliferation observed in tracheas cultured in CMRL-1066 medium are similar to the effects generally observed <em>in vivo</em> .<p>- The hamster tracheal organ culture model is very suitable to study the B[a]P-induced formation of DNA adducts and DNA-repair activities. Both the formation and repair of B[a]P-DNA adducts is dose and time dependent. Furthermore, the main adduct formed <em>in vitro</em> is similar to the adduct formed <em>in vivo</em> after intratracheal instillation of B[a]P, and moreover, this adduct is frequently observed in man.<p>- A high dietary dose of β-carotene, possibly in combination with a high level of et-tocopherol and ascorbyl palmitate, strongly increases the survival of hamsters.<p>- In tracheal epithelia] cells of hamsters treated intratracheally with B[a]P, a relationship between the level of B[a]P-DNA adducts, cell proliferation and p53 expression is observed.<p>- The effect of vitamin A on B[a]P-induced DNA-adduct formation and cell proliferation, as observed in the <em>in vitro</em> experiments, was not found in <em>in vivo</em> experiments, probably due to the high B[a]P dose applied.<p>- β-carotene did not affect the formation of (pre)neoplastic changes in the respiratory tract epithelium of hamsters intratracheally treated with B[a]P as evaluated by conventional histopathology, cytokeratin expression, and glutathione S-transferase isoenzyme Pi expression.<p>- Although intratracheal instillation of B[a]P to Syrian golden hamsters is one of the most widely applied models to study respiratory tract cancer in experimental animals, the tumour response is difficult to control due to a large number of variables affecting the response. The most important variables influencing the tumour response are the dose of B[a]P and the size of the B[a]P particles.<p>In conclusion, although the <em>in vitro</em> experiments described in this thesis show that vitamin A and β-carotene may influence the process of respiratory tract carcinogenesis, <em>in vivo</em> it was not possible to show a modulating effect of vitamin A and β-carotene on B[a]P-induced respiratory tract cancer in hamsters. To explain the inconsistencies in the effect of vitamin A and β-carotene on respiratory tract cancer, further in-depth research should he focused on the molecular mechanisms underlying this effect. The concentration of vitamin A and β-carotene, in particular the concentration of the active metabolite retinoic acid, in target cells should be measured in relation to the action of these molecules on the genomic level.
Mouse models in leukemia
Voncken, J.W. - \ 1995
Agricultural University. Promotor(en): R.W. Goldbach; J.H.C. Groffen. - S.l. : Voncken - ISBN 9789054854166 - 148
gammaretrovirus - virologie - moleculaire biologie - leukemie - muridae - muizen - modellen - onderzoek - virology - molecular biology - leukaemia - mice - models - research
<p>Human Philadelphia-positive leukemia results from a balanced chromosomal translocation, which fuses the <em>BCR</em> gene on chromosome 22 to the <em>ABL</em> proto-oncogene on chromosome 9. The understanding of Ph-positive leukemogenesis has advanced enormously over the last few decades. Although in vitro assay systems currently used, are not always relevant to human tumor biology, much can and has been learned from studies, employing cell cultures and overexpression of <em>BCR/ABL</em> oncogenes.<p>Another restriction in leukemia research is the availability of primary human tumor material for study. Moreover, such tissues often represent terminally advanced stages of tumorigenesis. Therefore, the importance of <em>in vivo</em> models to study Philadelphia-positive leukemia is manifold. A well defined transgenic mouse model allows for tumorigenesis to be studied from its earliest stages onward and factors and mechanisms that eventually contribute to malignant progression of the leukemic cells can be uncovered. Besides an 'unlimited' provision of tumor material for analysis, more importantly, the availability of a transgenic mouse model provides a means by which cancer treatment regimes can be tested. In addition, identification of cellular components and/or pathways that contribute to the onset or progression of leukemia may eventually lead to the discovery and development of new drugs.<p>In 1990, Heisterkamp and co-workers reported on a transgenic mouse model for Philadelphia-positive acute lymphoblastic leukemia (ALL). Since most of the transgenic animals of an earlier study had succumbed to leukemia, part of the aim of this thesis was to generate <em>BCR/ABL</em> P190 transgenic founder animals <em>de novo</em> and to derive a transgenic animal line(s) which was to be used for future studies. In order to better understand the animal model, leukemogenesis was studied in great detail in transgenic founder animals and their progeny. In the second chapter a cytogenetic study of the mouse model for acute lymphoblastic leukemia is presented. Karyotypic analysis of leukemic bone marrow of a significant number of mice shows, that leukemic cells undergo a clonal development and karyotype evolution toward a more aggressive tumor: a high frequency of aneuploidy is found in advanced leukemia, as occurs in human leukemia, with a preference for gain of chromosomes 10, 12, 14 and 17. These findings are corroborated by experiments that reveal a gain of malignancy of the cancer upon serial transplantation of leukemic bone marrow to irradiated recipient mice and by molecular analysis of lymphomas using immunoglobulin rearrangement as an indicator for tumor clonality. The results suggest that <em>BCR/ABL</em> has a destabilizing effect on the regulation of the proces of mitosis.<p>In the third chapter, a correlation is described between the transcriptional status of the <em>BCR/ABL</em> P190 transgene and the development of leukemia: methylation of particular sequences in <em>BCR</em> exon-1 in the transgene is closely coupled to transgene inactivation, providing additional evidence for a direct role of <em>BCR/ABL</em> in leukemogenesis. A biological dissection of the oncogenic specificity of <em>BCR/ABL is</em> presented in the fourth chapter. Using sensitive molecular biological techniques, it is shown that, although expression of the <em>BCR/ABL</em> transgene is detectable in every tissue, from very early on in mouse development, no other neoplasias than of hematopoietic origin are found. The results strongly suggest that the oncogenicity of <em>BCR/ABL</em> is restricted to nucleated blood cells, which is very likely a reflection of cellular functions of the <em>BCR</em> and or <em>ABL</em> gene in signal transduction specific to hematopoietic lineages. The observations would also explain why the Ph-chromosome, which one would expect to arise by chance in many proliferating tissues, is found only in blood cancers.<p>An analysis of transgenic mouse models for chronic myelogenous leukemia, using <em>BCR/ABL</em> P210 transgenes is presented in the fifth chapter. The clinical disease spectrum includes differentiated and undifferentiated T and B cell leukemias. The myeloid compartment is implicated only sporadically and rather late in the disease process. In some instances, the observed myelo-proliferation is a sequel to deregulation of cytokine production at advanced stages of leukemia. The course of P210 induced leukemia was acute rather than chronic, be it with an on average longer latency period than typical for ALL in <em>BCR/ABL</em> P190 mice. From these studies is was concluded that in the mouse, <em>BCR/ABL</em> P210 evokes a clinically different disease than <em>BCR/ABL</em> P190. Although no evidence for a chronic myeloproliferative disorder in the peripheral blood was found, an imbalance in myelopoiesis in the bone marrow suggests an effect of <em>BCR/ABL</em> P210 on primitive myeloid progenitors.<p>The sixth chapter summarizes an analysis of interferon-α(IFN-α) treatment of the <em>BCR/ABL P190</em> transgenic mice. (IFN-α) is currently one of the most effective drugs in the treatment of CML. Recently, (IFN-α) was tried in the treatment of ALL. No effect of (IFN-α) on animal survival or disease pattern were noted when administered to the <em>BCR/ABL P190</em> mice. The conclusion was reached that, at least in a transgenic setting, (IFN-α) does not interfere with <em>BCR/ABL</em> P190 mediated leukemia.<p>In order to study the normal cellular function of the <em>BCR</em> gene and to eventually assess its role in leukemogenesis, studies focussing on the mouse <em>bcr</em> gene function are presented in chapters 7 and 8. The seventh chapter describes the ablation of a functional mouse <em>bcr</em> gene by means of recently developed gene targeting techniques. One of two mouse <em>bcr</em> alleles was inactivated in a mouse embryonic stem cell line through gene interruption by insertional replacement vectors. Ibis genetically altered cell fine was then injected into developing mouse embryos. Through germline transmission of the mutated allele and subsequent breeding both <em>bcr</em> alleles were inactivated. Although <em>bcr</em> -null mutants are phenotypically normal, their neutrophils display impaired regulation of respiratory burst, which becomes apparent when these cells are activated <em>in vivo:</em> an overproduction of superoxide leads to significantly more oxidative tissue damage during experimental endotoxemia. The results connect Bcr <em>in vivo</em> with the regulation of superoxide production by the NADPH- oxidase system of leukocytes and suggest a link between the cell types affected by loss of Bcr function and the those involved in <em>Ph</em> -positive leukemia.<p>Additional information on biological processes that Bcr participates in, are described. in the eighths chapter. Notwithstanding its function in hematopoietic cells, the Bcr protein is normally found in high levels in brain. The expression pattern of bcr in rodent brain was examined by means of <em>in situ</em> hybridization and Northern analysis. Although not directly connected with leukemogenesis, a potentially interesting role for p160Bcr in the brain is discussed as its expression pattern appears to coincide with the functional organization of particularly highly specialized structures in the brain.<p>With the availability of well defined transgenic mouse models for <em>BCR/ABL</em> positive leukemia, an opportunity is created to study the nature of cellular interactions and processes that contribute to the onset and development of <em>Ph</em> -positive leukemia. Ultimately, such investigations are aimed at designing and testing effective therapeutic drugs to fight the disease.
Molmuis ondergraaft vegetatie-ontwikkeling.
Kooy, J. van der; Maanen, B. van - \ 1994
Zoogdier 5 (1994)2. - ISSN 0925-1006 - p. 3 - 7.
dieren - begrazing - herbivoren - muizen - muridae - plantensuccessie - ratten - verstoring - limburg - animals - grazing - herbivores - mice - plant succession - rats - disturbance
Prevention of vole damage on trees : a review of literature
Moraal, L.G. - \ 1993
Wageningen : IBN-DLO (IBN research report 93/7) - 14
bosschade - wilde dieren - muridae - muizen - ratten - bosbouw - fysische gewasbeschermingsmethoden - gewasbescherming - rodenticiden - overzichten - schadelijke dieren - mechanische bestrijding - forest damage - wild animals - mice - rats - forestry - physical control - plant protection - rodenticides - reviews - noxious animals - mechanical control
Zygote development after delayed fertilization : a cytological and genetical analysis of embryos of the mouse
Boerjan, M.L. - \ 1990
Agricultural University. Promotor(en): C. Heyting; P. de Boer. - S.l. : Boerjan - 90
muridae - muizen - geomyidae - eieren - ontwikkeling - eivorming - oögenese - dierlijke weefsels - beenweefsel - dieranatomie - mice - eggs - development - egg formation - oogenesis - animal tissues - bone tissue - animal anatomy
<p><TT><strong>Chapter I</strong> gives (1) a brief review of morphological and molecular changes in mammalian oocytes initiated by fertilization, (2) a summary of published data on several aspects of post-ovulatory ageing in relation to embryonic development and (3) a description of methods to time ovulation and fertilization.</TT><p><TT>Precise timing of ovulation and fertilization was a prerequisite for the study of the consequences of delayed fertilization for embryonic development.</TT><br/><TT><strong>Chapter II</strong> describes the methods of ovulation induction and artificial insemination. We induced ovulation with injections of luteinizing hormone releasing hormone (LHRH) at pro-oestrus of the oestrus cycle. The number of oocytes that ovulated after LHRH administration was similar to that after spontaneous ovulation. Although LHRH was administered 8-12 hrs before the expected endogenous luteinizing hormone (LH) surge, we found no significant effect of LHRH induced ovulation on embryonic mortality. This method of ovulation induction, supplemented with artificial insemination to achieve <em>in vivo</em> fertilization, provided a tool to study aspects of early embryonic development after delayed fertilization.</TT><p><TT>Investigations were carried out to determine in detail the timing of the distinct morphological changes triggered by fertilization of unaged oocytes and oocytes aged post-ovulation for 12 hrs. Sperm penetration was shown to be accelerated by 1 hr 30 min after delayed insemination compared with sperm penetration in unaged oocytes. The rate of progression to the first cleavage division was also influenced by the post-ovulation age of mouse oocytes prior to fertilization: penetrated aged oocytes needed less time (1 hr 30 min) to reach the 2-cell stage than zygotes from unaged oocytes. This observation was confirmed by experiments carried out later: the percentages of 3- and 4-cell embryos from aged and unaged oocytes, collected 36 hrs after insemination, were 14% and 7% respectively (Chapter IV).</TT><p><TT>Fertilization activates, among other things, a cascade reaction of protein synthetic alterations.</TT><br/><TT><strong>Chapter III</strong> deals with protein synthetic activity in unaged and aged LHRH induced oocytes, in unaged superovulated oocytes and in zygotes derived from these types of oocytes. Polypeptides with a relative molecular weight of 35 kDa were predominantly synthesized by LHRH induced and superovulated secondary oocytes and zygotes from these oocytes. This study of patterns of 35 kDa proteins synthesized by zygotes from aged and unaged LHRH induced oocytes revealed that fertilization dependent protein synthetic changes of the 35 kDa protein complex were advanced in zygotes from aged oocytes with reference to pronuclear development.</TT><br/><TT>A fraction (16.7%) of morphologically normal zygotes from unaged superovulated oocytes did not synthesize the 35 kDa protein complex at all.</TT><p><TT>It was of interest to learn more about the in vitro developmental capacity of embryos from aged oocytes.</TT><br/><TT>In <strong>Chapter IV</strong> the results of these investigations are arranged and discussed. One-cell and late 2-cell embryos from aged and unaged oocytes were cultured in the presence and absence of DNA damage or DNA-damaging agents for different periods of time. On the one hand we studied the progression to metaphase of the first cleavage division in zygotes from aged and unaged oocytes fertilized with X-irradiated sperm. On the other hand the in vitro developmental capacity of late 2-cell embryos was evaluated in presence and absence of the thymidine analogue 5-Bromode-oxyuridine (BrdU).</TT><p><TT>Post-ovulatory ageing had an effect on the morphology of male as well as female pronuclear chromosomes of the first cleavage metaphase. We also found a detrimental effect of fertilization with X-irradiated spermatozoa on the morphology of male and female pronuclear chromosomes. This effect was particularly observed in male pronuclear chromosomes of zygotes from aged oocytes. Furthermore, fertilization with X-irradiated spermatozoa led to an arrest at interphase in 27% and 7% of zygotes from aged and unaged oocytes respectively. This arrest was not shown after fertilization with sperm not irradiated with X-rays.</TT><p><TT>This experimental setup also enabled us to compare the amount of radiation induced chromosome damage in zygotes from aged and unaged oocytes. Zygotes from aged oocytes did not contain more chromosome damage than zygotes from unaged oocytes, when the visible chromosome mutations originating from the X-irradiated spermatozoa were analyzed at metaphase of the first cleavage division.</TT><br/><TT>In <strong>Chapter IV</strong> we also have shown that zygotes from aged oocytes and unaged oocytes develop in vitro at similar rates from the late 2-cell stage, collected at 36 hrs after insemination, to the 8-cell stage (24 hrs cultures). However, <em>in vitro</em> development of 2-cell embryos from aged oocytes collected 30 hrs after insemination and cultured for 66 hrs is impaired.</TT><br/><TT>To determine the number of sister-chromatid exchanges, we cultured 2-cell embryos from aged and unaged oocytes, collected 36 hrs after insemination, in the presence of BrdU for 24 hrs. SCE levels were not significantly different between embryos from aged and unaged oocytes.</TT><br/><TT>Cell proliferation of late 2-cell embryos from aged oocytes, collected 36 hrs post-insemination, from aged oocytes was clearly retarded and asynchronous during the 24 hrs culture period in the presence of 10-6 M BrdU.</TT><p><TT>In <strong>Chapter V</strong> a cytochemical method is described to determine in individual oocytes the distribution of the activity of SDH (succinate dehydrogenase), an enzyme which is located on the inner membrane of mitochondria. We showed that treatment of oocytes with the drug caffeine prior to cytochemical staining resulted in an intens staining of the cells by a formazan precipitate. We applied the cytochemical staining procedure to preovulatory oocytes of mice. In a maturation experiment in vitro we found that the location of formazan correlated well with the location of mitochondria in subsequent stages of maturation. Unfortunately, this cytochemical staining procedure could not be applied to ovulated and fertilized oocytes, since these cells acquired a poor morphology during the staining procedure and displayed high levels of non -dehydrogenase formazan production.</TT>
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