1. Mamm Genome. 1999 Sep;10(9):883-7.
BB rat diabetes susceptibility and body weight regulation genes colocalize on
chromosome 2.
Klaff LS(1), Koike G, Jiang J, Wang Y, Bieg S, Pettersson A, Lander E, Jacob H,
Lernmark A.
Author information:
(1)R.H. Williams Laboratory, Department of Medicine, University of Washington,
1959 N.E. Pacific Street, Box 357710, Seattle, Washington 98195, USA.
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 F(2)
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 F(2)N(2) progeny in
a cross between non-diabetic F(2)(DR(lyp/lyp,u/u) x 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.
PMID: 10441739 [PubMed - indexed for MEDLINE]
PUBMED: 10441739
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