BB rat diabetes susceptibility and body weight regulation genes colocalize on Chromosome 2 |
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Authors: | Lindy S Klaff George Koike Jianjie Jiang Yanling Wang Sabine Bieg Anna Pettersson Eric Lander Howard Jacob Åke Lernmark |
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Institution: | (1) R.H. Williams Laboratory, Department of Medicine, University of Washington, 1959 N.E. Pacific Street, Box 357710, Seattle, Washington 98195, USA, US;(2) Cardiovascular Research Center, Massachusetts General Hospital-East, 149-13th Street, Charlestown, Massachusetts 02129, USA, US;(3) Medical College of Wisconsin, Department of Physiology, 8701 Watertown Plank Road, P.O. Box 26509, Milwaukee, Wisconsin 53226, USA, US;(4) Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, Massachusetts, USA, US |
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Abstract: | The genetic etiology of Type 1 (insulin-dependent) diabetes mellitus is complicated by the apparent presence of several diabetes
susceptibility genetic regions. Type 1 diabetes in the inbred BioBreeding (BB) rat closely resembles the human disorder and
was previously shown to involve two genes: the lymphopenia (lyp) region on Chromosome (Chr) 4 and RT1
u
in the major histocompatibility complex (MHC) on Chr 20. In addition, a segregation analysis of an F2 intercross between the diabetes-prone congenic BB DR
lyp/lyp,u/u
and F344+/+,
lv/lv
rats indicated that at least one more genetic factor was responsible for Type 1 diabetes. In this study, we generated F2N2 progeny in a cross between non-diabetic F2(DR
lyp/lyp,u/u
× F344)
lyp/lyp,u/u
and diabetic DR
lyp/lyp,u/u
rats. In a subsequent total genome scan, a third factor was mapped to the 21.3-cM region on Chr 2 between D2Mit14 and D2Mit15 (peak LOD score 4.7 with 67% penetrance). Interestingly, the homozygosity of the BB allele (b/b) for the Chr 2 region was significantly associated with a greater weight reduction after fasting than the homozygosity of
the F344 allele (f/f, p < 0.008). In conclusion, the development of Type 1 diabetes in the congenic DR
lyp/lyp
rat is controlled by at least three genes: lymphopenia, MHC, and a third factor that may play a role in metabolism and body
weight regulation.
Received: December 1998 / Accepted: 10 May 1999 |
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Keywords: | |
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