International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 38 - CONSTRUCTION AND CHARACTERIZATION OF THE CONGENIC STRAINS DERIVED FROM THE OBESE DIABETES MOUSE, TSOD

Dr. Shin Mizutani
Gunma University, JAPAN
3-39-15 Showa-machi
Maebashi 371-8512
JAPAN

Co-Authors: Hirayama I, Izumi T
Institutions: Institute for Molecular and Cellular Regulation, Gunma University

The TSOD (Tsumura, Suzuki, Obese Diabetes) mouse, a newly developed animal model, exhibits both diabetes and obesity with marked hyperinsulinemia and hypertrophy of the pancreatic islet and might represent a common form of obese type 2 diabetes in humans.  A genome-wide screen for loci linked to glucose homeostasis and body weight allowed us to map three quantitative loci (QTLs) involved in this disorder.  The major genetic determinant of blood glucose levels was identified on chromosome 11 (Nidd 4).  Furthermore, two independent QTLs involved in controlling body weight were found on chromosome 1 (Nidd 6) and 2 (Nidd 5).  The QTL on chromosome 2 also affected insulin levels significantly (Hirayama et al., Diabetes, 48: 1183, 1999).

Recently, we constructed three congenic strains, TSOD/Nidd4, TSOD/Nidd5, and TSOD/Nidd6, in which each QTL regions from Balb/c (as a control lean mouse) was transferred to TSOD.  Although TSOD/Nidd4 was as heavy as TSOD, they exhibited the lower plasma glucose levels after intraperitoneal glucose tolerance test.  Consistent with the genetic analysis, the body weight of TSOD/Nidd5 and TSOD/Nidd6 were less than TSOD.  These results indicate that hyperglycemia and obesity are clearly controlled by distinct combination of genetic loci in TSOD, and provides insights into the genetic basis of common forms of human type 2 diabetes with obesity.


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