RGD Reference Report - BB rat diabetes susceptibility and body weight regulation genes colocalize on chromosome 2. - Rat Genome Database

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BB rat diabetes susceptibility and body weight regulation genes colocalize on chromosome 2.

Authors: Klaff, LS  Koike, G  Iang J, J  Wang, Y  Bieg, S  Pettersson, A  Lander, E  Jacob, H  Lernmark, A 
Citation: Klaff LS, etal., Mamm Genome 1999 Sep;10(9):883-7
RGD ID: 61481
Web Url: http://link.springer-ny.com/link/service/journals/00335/bibs/10n9p883.html
Pubmed: (View Article at PubMed) PMID:10441739

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.

Annotation

Objects Annotated

QTLs
Iddm3  (Insulin dependent diabetes mellitus QTL 3)

Objects referenced in this article
Strain BBDR/Rhw null Rattus norvegicus
Strain F344/NRrrc null Rattus norvegicus
QTL Iddm2 Insulin dependent diabetes mellitus QTL 2 Rattus norvegicus

Additional Information