TY - JOUR
T1 - BB rat diabetes susceptibility and body weight regulation genes colocalize on Chromosome 2
AU - Klaff, Lindy S.
AU - Koike, George
AU - Jiang, Jianjie
AU - Wang, Yanling
AU - Bieg, Sabine
AU - Pettersson, Anna
AU - Lander, Eric
AU - Jacob, Howard
AU - Lernmark, Ake
PY - 1999/9/30
Y1 - 1999/9/30
N2 - The genetic etiology of Type 1 (insulin-dependent) diabetes mellitus is complicated by the apparent presence of several diabetes susceptibility genetic regions. Type I 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) 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 I 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.
AB - The genetic etiology of Type 1 (insulin-dependent) diabetes mellitus is complicated by the apparent presence of several diabetes susceptibility genetic regions. Type I 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) 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 I 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.
U2 - 10.1007/s003359901108
DO - 10.1007/s003359901108
M3 - Article
C2 - 10441739
AN - SCOPUS:0032878618
SN - 0938-8990
VL - 10
SP - 883
EP - 887
JO - Mammalian Genome
JF - Mammalian Genome
IS - 9
ER -
