Genetic analysis for diabetes in a new rat model of nonobese type 2 diabetes, Spontaneously Diabetic Torii rat.
The Spontaneously Diabetic Torii (SDT) rat has recently been established as a new rat model of nonobese type 2 diabetes. In this study, we characterized diabetic features in SDT rats, and performed quantitative trait locus (QTL) analysis for glucose intolerance using 319 male (BNxSDT)xSDT backcrosses. Male SDT rats exhibited glucose intolerance at 20 weeks, and spontaneously developed diabetes with the incidence of 100% at 38 weeks, and glucose intolerance is well associated with the development of diabetes. The QTL analysis identified three highly significant QTLs (Gisdt1, Gisdt2, and Gisdt3) for glucose intolerance on rat chromosomes 1, 2, and X, respectively. The SDT allele for these QTLs significantly exacerbated glucose intolerance. Furthermore, synergistic interactions among these QTLs were detected. These findings indicate that diabetic features in SDT rats are inherited as polygenic traits and that SDT rats would provide insights into genetics of human type 2 diabetes.
Masuyama
Taku
T
Laboratory of Veterinary Anatomy, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka, 020-8550, Iwate, Japan. t.masuyama@tba.t-com.ne.jp <t.masuyama@tba.t-com.ne.jp>
Fuse
Masanori
M
Yokoi
Norihide
N
Shinohara
Masami
M
Tsujii
Hirotada
H
Kanazawa
Masao
M
Kanazawa
Yasunori
Y
Komeda
Kajuro
K
Taniguchi
Kazuyuki
K
D017668:Age of Onset; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005838:Genotype; D018149:Glucose Intolerance / Q000097:blood / Q000235:genetics; D008297:Male; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose