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Summary: 1946 DIABETES, VOL. 49, NOVEMBER 2000
Genetic Obesity Unmasks Nonlinear Interactions
Between Murine Type 2 Diabetes Susceptibility Loci
Jonathan P. Stoehr, Samuel T. Nadler, Kathryn L. Schueler, Mary E. Rabaglia, Brian S. Yandell,
Stewart A. Metz, and Alan D. Attie
Nonlinear interactions between obesity and genetic
risk factors are thought to determine susceptibility to
type 2 diabetes. We used genetic obesity as a tool to
uncover latent differences in diabetes susceptibility
between two mouse strains, C57BL/6J (B6) and BTBR.
Although both BTBR and B6 lean mice are euglycemic
and glucose tolerant, lean BTBR B6 F1 male mice
are profoundly insulin resistant. We hypothesized that
the genetic determinants of the insulin resistance syn-
drome might also predispose genetically obese mice to
severe diabetes. Introgressing the ob allele into BTBR
revealed large differences in diabetes susceptibility
between the strain backgrounds. In a population of F2-
ob/ob mice segregating for BTBR and B6 alleles, we
observed large variation in pancreatic compensation
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