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Genetic and Genomic Studies of the BTBR ob/ob Mouse Model of Type 2 Diabetes
 

Summary: Genetic and Genomic Studies of the BTBR ob/ob
Mouse Model of Type 2 Diabetes
Susanne M. Clee, Samuel T. Nadler, and Alan D. Attie*
The BTBR mouse strain harbors alleles promoting insulin resistance. When made genetically obese
(ob/ob), these mice develop severe type 2 diabetes (fasting glucose .400 mg/dL). By contrast,
C57BL/6 ob/ob mice are able to compensate for the obesity-induced insulin resistance by increasing
pancreatic insulin secretion and thus maintain only slightly elevated plasma glucose levels (,250
mg/dL). Islet insulin secretory responses to glucose are undiminished in the remaining islets of BTBR
ob/ob mice. A genome-wide linkage analysis identified 3 major loci influencing plasma glucose and/or
insulin levels in an F2ob/ob sample derived from the 2 strains. A locus on chromosome 2 affects
insulin sensitivity and is independent of obesity. Loci on chromosomes 16 and 19 affect fasting
glucose and insulin levels and likely affect b-cell mass or function. Analysis of mRNA expression
patterns revealed a reduction in lipogenic gene expression in adipose tissue associated with obesity.
Conversely, hepatic lipogenic gene expression increases in obese mice, but to a much greater extent in
the diabetes-resistant C57BL/6 strain. We propose that hepatic lipogenic capacity affects
susceptibility to obesity-induced diabetes.
Keywords: type 2 diabetes, BTBR, insulin resistance, obesity, pancreatic decompensation, genetics,
QTL, microarrays
INTRODUCTION
Type 2 diabetes (DM2) is a progressive disease that

  

Source: Attie, Alan D. - Department of Biochemistry, University of Wisconsin at Madison

 

Collections: Biology and Medicine