BB rat diabetes susceptibility and body weight regulation genes colocalize on chromosome 2. Mamm Genome 1999 Sep;10(9):883-7
Date
08/12/1999Pubmed ID
10441739DOI
10.1007/s003359901108Scopus ID
2-s2.0-0032878618 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
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.
Author List
Klaff LS, Koike G, Jiang J, Wang Y, Bieg S, Pettersson A, Lander E, Jacob H, Lernmark AMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Congenic
Body Weight
Chromosome Mapping
Crosses, Genetic
Diabetes Mellitus, Type 1
Female
Humans
Male
Phenotype
Rats
Rats, Inbred BB
Rats, Inbred F344
