Rats are an important experiment model for many human diseases, many of which have a genetic component. As followup of our previous work demonstrating impressive differences in the phenotypic responses of LEW and F344 rats to various proinflammatory and noninflammatory stimuli, we have begun to develop a genetic linkage map for rats, specifically applicable to these rat strains. We have now identified about 190 polymorphisms that differ in these rat strains and have mapped most of these to specific chromosomes or linkage groups. We have observed impressive conservation of synteny between rat, mouse and human chromosomes. In addition to beginning a study of cosegregation of inflammatory arthritis with the various polymorphisms in F2 intercross progeny of LEW and F344 rats, we studied the segregation of the athymic nude trait in F2 intercross progeny of athymic nude LEW x euthymic F344 rats. We mapped the locus that controls the nude phenotype to rat chromosome 19m approximately 4 cM from the myosin heavy chain locus. Moreover, through extensive genotyping of 11 additional rat strains, we demonstrated that the LER rat arose as an outcross between LEW and BUF rats, and not, as originally reported, as a spontaneous mutation in LEW rats.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Dracheva, S V; Remmers, E F; Chen, S et al. (2000) An integrated genetic linkage map with 1,137 markers constructed from five F2 crosses of autoimmune disease-prone and -resistant inbred rat strains. Genomics 63:202-26
Brodkin, E S; Kosten, T A; Haile, C N et al. (1999) Dark Agouti and Fischer 344 rats: differential behavioral responses to morphine and biochemical differences in the ventral tegmental area. Neuroscience 88:1307-15
Joe, B; Griffiths, M M; Remmers, E F et al. (1999) Animal models of rheumatoid arthritis and related inflammation. Curr Rheumatol Rep 1:139-48
Shepard, J S; Remmers, E F; Chen, S et al. (1999) A genetic linkage map of rat Chromosome 15 derived from five F2 crosses. Mamm Genome 10:186-8
Dracheva, S V; Remmers, E F; Gulko, P S et al. (1999) Identification of a new quantitative trait locus on chromosome 7 controlling disease severity of collagen-induced arthritis in rats. Immunogenetics 49:787-91
Wilder, R L; Griffiths, M M; Remmers, E F et al. (1999) Localization in rats of genetic loci regulating susceptibility to experimental erosive arthritis and related autoimmune diseases. Transplant Proc 31:1585-8
Griffiths, M M; Remmers, E F; Cannon, G W et al. (1999) MHC and non-MHC genes in the regulation of susceptibility to collagen-induced arthritis among DA, BB, and BN rats. Transplant Proc 31:1589
Remmers, E F; Griffiths, M M; Longman, R E et al. (1999) An integrated rat genetic map: analysis of linkage conservation with the mouse and human maps. Transplant Proc 31:1549-54
Sun, S H; Silver, P B; Caspi, R R et al. (1999) Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats. Int Immunol 11:529-34
Griffiths, M M; Encinas, J A; Remmers, E F et al. (1999) Mapping autoimmunity genes. Curr Opin Immunol 11:689-700