{"title":"Phenotypic selection: a successful strategy to fix major genes of hypertension","authors":"P. Kovács, J. van den Brandt, I. Klöting","doi":"10.1016/S0939-8600(00)80032-2","DOIUrl":"10.1016/S0939-8600(00)80032-2","url":null,"abstract":"<div><p>Spontaneously diabetic BB/OK rats are not genetically susceptible to develop diabetic complications as hypertension or nephropathy. Recently, we generated 5 congenic BB. SHR rat strains by transferring different chromosomal regions of the spontaneously hypertensive rat (SHR) onto the genetic background of BB/OK rats. Four out of 5 strains showed a weak increase of blood pressure (8 mmHg). This weak blood pressure effect indicated that the transferred regions fo not contain major genes for hypertension. That prompted us to choose the classical procedure of phenotypic selection to fix major genes causing hypertension in a BB/OK rat subline generated by cross of BB/OK and SHR and repeated backcrossing of animals with highest blood pressure onto normotensive BB/OK rats. After 7 backcrosses (N8), all backcross parents were genetically analysed with the aid of 259 microsatellites to identify loci causing blood pressure of 177 ± 10 mmHg in this BB/OK rat subline. The data revealed, that loci on chromosome 1, 14 and 18 were heterozygous until BC5, BC6 and BC7, respectively. Considering the relative stable high blood pressure during the backcross procedure, these loci might be of essential importance for the development of hypertension in the SHR.</p></div>","PeriodicalId":77206,"journal":{"name":"Journal of experimental animal science","volume":"41 1","pages":"Pages 61-63"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0939-8600(00)80032-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84098639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic analysis of hypertension in the Dahl salt-sensitive rat","authors":"J.P. Rapp","doi":"10.1016/S0939-8600(00)80017-6","DOIUrl":"10.1016/S0939-8600(00)80017-6","url":null,"abstract":"<div><p>Quantitative trait loci (QTL) for blood pressure were sought using crosses of Dahl salt sensitive (S) rats and various normotensive strains. Multiple QTL were detected by linkage analysis and these were confirmed by construction of congenic strains for the QTL on chromosomes 1, 2, 3, 5, 7, 9, 10 and 13.</p></div>","PeriodicalId":77206,"journal":{"name":"Journal of experimental animal science","volume":"41 1","pages":"Pages 5-6"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0939-8600(00)80017-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56856787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Knoblauch , C. Gösele , H. Zimdahl , B. Hieke , H. Himmelbauer , L. Schalkwyk , K. Lindpaintner , D. Ganten , H. Lehrach
{"title":"New tools for the high throughput characterization of rat genomic DNA samples","authors":"M. Knoblauch , C. Gösele , H. Zimdahl , B. Hieke , H. Himmelbauer , L. Schalkwyk , K. Lindpaintner , D. Ganten , H. Lehrach","doi":"10.1016/S0939-8600(00)80024-3","DOIUrl":"10.1016/S0939-8600(00)80024-3","url":null,"abstract":"<div><p>Linkage studies and positional cloning projects for the identification of disease related genes require the genetic characterization of large numbers of genomic DNA samples. The application of spotting robots enables the production of high density filters representing several thousand DNA probes. To take full advantage of the potential of these filters we have established a new, hybridization based Interspersed Repetitive Sequence (IRS-)marker system for the rat genome. This marker panel was shown to be useful for rapid genotyping of many multigenic crosses as well as high throughput characterization of large insert genomic libraries.</p></div>","PeriodicalId":77206,"journal":{"name":"Journal of experimental animal science","volume":"41 1","pages":"Pages 35-37"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0939-8600(00)80024-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56856881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drahomíra Křenová , Zuzana Jirsová , Vlasta Bílá , Rudolf Kašpárek , Michal Pravenec , Vladimír Křen
{"title":"Genetics of rat hypodactyly","authors":"Drahomíra Křenová , Zuzana Jirsová , Vlasta Bílá , Rudolf Kašpárek , Michal Pravenec , Vladimír Křen","doi":"10.1016/S0939-8600(00)80028-0","DOIUrl":"10.1016/S0939-8600(00)80028-0","url":null,"abstract":"<div><p>Rat hypodactyly was originally described by <span>Moutier</span> et al. (1973) as an autosomal recessive trait. The determining gene <em>Hd</em> has been recently mapped to rat chromosome 10 and is closely linked to the <em>D10Rat31/32, D10Rat30</em>, and <em>Myh3 loci</em> (<span>Křenová</span> et al. 1998). In homozygous state <em>(Hd/Hd)</em>, there is a variable reduction in the number of fingers and metacarpals — metatarsals of front and hind feet in males and females. Moreover, there is a male sterility in homozygotes whereas male heterozygotes are fertile. The light and electron microscopic examination confirmed disorder of spermatogenesis, loosening and vacuolization of seminiferous epithelium accompanied with a significantly decreased number of germ cells in testes of homozygotes.</p><p>In an intercross population (Wistar Hd×BN-Lx)F2, an independent segregation of the major genes <em>Lx</em>, coding for the PLS (polydactyly-luxate syndrome), and <em>Hd</em> — hypodactyly was found together with irregular interactions of <em>Hd</em> and <em>Lx</em> genes in double homozygotes (<em>Hd/Hd, Lx/Lx</em>). The variable phenotype manifestation of foot malformation in double homozygous animals indicated modifying influences of genes of the genetic background. In order to study more precisely the role of the determining major gene <em>Hd</em> as well as the role of the putative modifying genes in the development of the foot malformation and male sterility, we started the production of two congenic strains by introgressing the <em>Hd</em> mutant gene onto the genetic backgrounds of the BN and SHR inbred strains.</p></div>","PeriodicalId":77206,"journal":{"name":"Journal of experimental animal science","volume":"41 1","pages":"Pages 47-50"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0939-8600(00)80028-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56856916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Polygenetic susceptibility and resistance to 4-nitroquinoline 1-oxide-induced tongue carcinomas in the rat","authors":"Jun-ichi Tanuma , Motoo Kitano , Hayase Shisa , Hiroshi Hiai","doi":"10.1016/S0939-8600(00)80034-6","DOIUrl":"10.1016/S0939-8600(00)80034-6","url":null,"abstract":"<div><p>Oral administration of 4-nitroquinoline 1-oxide (4NQO) to rats induced a high incidence of tongue carcinomas (TCs). The inbred Dark-Agouti (DA) strain of rats showed much higher susceptibility to 4NQO-induced TCs than the Wistar-Furth (WF) strain. Our previous study on crosses between the two strains postulated a semidominant susceptibility gene in DA and a semidominant resistance gene in WF rats. This hypothesis was confirmed by the genetic analysis of the back-crosses to either parent with PCR-based microsatellite assay. Using the number of TCS with >5 mm diameter as a quantitative parameter, we mapped a quantitative trait locus <em>Stc1 (Susceptibility to TC)</em> favouring TC development near the locus <em>D19Mit9</em> on Chr. 19 with a peak LOD score of 6.08. Two other regions in Chr. 3 and Chr. 14 showed weak linkage for susceptibility, but were not statistically significant. On the other hand, another quantitative trait locus <em>Rtc1 (Resistance to TC)</em> providing resistance to TCs was mapped on Chr. 1 between the loci of <em>D1Mit1</em> and <em>D1Mit3</em> with a peak LOD score of 3.30. Quantitative parameters such as the number of tumours in the tongue or upper alimentary tract, the frequency of larger tumours and their maximum size were closely correlated and principally determined by <em>Stc1</em> and <em>Rtc1</em>. Therefore the susceptibility to 4NQO-induced TCs in crosses between DA and WF is explained by the combinations of genotypes at these two loci. Possible candidate genes for <em>Stc1</em> and <em>Rtc1</em> are discussed.</p></div>","PeriodicalId":77206,"journal":{"name":"Journal of experimental animal science","volume":"41 1","pages":"Pages 68-77"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0939-8600(00)80034-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56857142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hans-Peter Raué, Flip Klatter, Machteld Hylkema, Margaretha van der Deen, Herman Groen, Jennie Pater, Paul Nieuwenhuis, Auk Hardonk-Wubbena, Jan-Luuk Hillebrands, Jan Rozing
{"title":"Efficiency of intrathymic tolerance induction in various inbred rat strains: relationship with TH1/TH2 status of the recipient?","authors":"Hans-Peter Raué, Flip Klatter, Machteld Hylkema, Margaretha van der Deen, Herman Groen, Jennie Pater, Paul Nieuwenhuis, Auk Hardonk-Wubbena, Jan-Luuk Hillebrands, Jan Rozing","doi":"10.1016/S0939-8600(00)80036-X","DOIUrl":"10.1016/S0939-8600(00)80036-X","url":null,"abstract":"<div><p>The simultaneous transplantation and intrathymic tolerance induction (STITTI) protocol induces a longlasting state of functional tolerance in over 90% of AO (RT1<sup>u</sup>) recipients transplanted with a fully MHC-incompatible PVG (RT1<sup>c</sup>) cardiac allograft. Similar results are obtained when using LEWIS (RT1<sup>1</sup>) rats as recipients of either PVG or DA (RT1<sup>avl</sup>) grafts. However, when STITTI is performed on PVG and BN (RT1<sup>n</sup>) as recipient animals receiving spleen cells intrathymically and a cardiac allograft from respectively AO and PVG rats, this procedure results in significantly shorter graft survival (MST PVG → BN 25 ± 9 days; AO → PVG 31 ± 8 days) as compared to the combinations using AO (MST PVG → AO > 236 ± 28 days) and LEWIS (MST PVG → LEW > 366 ± 51 days; DA → LEW > 123 ± 33 days) rats as recipients. Since both PVG and BN rats are relatively deficient in their ability to produce IFNγ and intrathymic IFNγ responses are very dominant upon intrathymic injection of alloantigens, it is argued that the inability to effectively induce a longlasting state of functional tolerance in BN and PVG rats using the STITTI protocol may be related to their decreased IFNγ-production potential.</p></div>","PeriodicalId":77206,"journal":{"name":"Journal of experimental animal science","volume":"41 1","pages":"Pages 82-86"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0939-8600(00)80036-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56857359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Claude Szpirer , Josiane Szpirer , Pascale Vanvooren , Fadel Tissir , Johanna Kela , Francoise Lallemand , Barbara Hoebee , Jason S. Simon , George Koike , Howard J. Jacob , Eric S. Lander , Khalil Helou , Karin Klinga-Levan , Göran Levan
{"title":"The rat genetic and cytogenetic maps","authors":"Claude Szpirer , Josiane Szpirer , Pascale Vanvooren , Fadel Tissir , Johanna Kela , Francoise Lallemand , Barbara Hoebee , Jason S. Simon , George Koike , Howard J. Jacob , Eric S. Lander , Khalil Helou , Karin Klinga-Levan , Göran Levan","doi":"10.1016/S0939-8600(00)80025-5","DOIUrl":"10.1016/S0939-8600(00)80025-5","url":null,"abstract":"<div><p>The rat map was improved by determining the regional chromosome localization of 82 genes, thereby orienting each linkage group. New anonymous markers were also generated on rat chromosome 2.</p></div>","PeriodicalId":77206,"journal":{"name":"Journal of experimental animal science","volume":"41 1","pages":"Pages 38-39"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0939-8600(00)80025-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56856612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Determination of the mouse homologous region for the rat dmy locus","authors":"Kazuhiro Kitada , Jean-Louis Guénet , Tadao Serikawa","doi":"10.1016/S0939-8600(00)80026-7","DOIUrl":"10.1016/S0939-8600(00)80026-7","url":null,"abstract":"<div><p>The autosomal recessive mutation <em>dmy</em> causes neurological changes which are characterized by a severe demyelination in the spinal cord, associated with paralysis of the hind limbs. Kuramoto et al. have already mapped the mutation between <em>Hh1ltts</em> and <em>Agtr1a</em> loci on rat chromosome 17 (Kuramoto et al. 1996). Toward the identification of the <em>dmy</em> mutation, we determined here the corresponding genomic region on mouse chromosome 13 and constructed its fine genetic and physical maps. We are currently producing further backcross progeny to narrow down the <em>dmy</em> interval on the rat genome. Determination of the homologous region on the mouse genome should help identifying the causative gene.</p></div>","PeriodicalId":77206,"journal":{"name":"Journal of experimental animal science","volume":"41 1","pages":"Pages 40-43"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0939-8600(00)80026-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56856690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}