Type 2 diabetes-like hyperglycemia in a backcross model of NZO and SJL mice: characterization of a susceptibility locus on chromosome 4 and its relation with obesity

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Item Type:	Article
Title:	Type 2 diabetes-like hyperglycemia in a backcross model of NZO and SJL mice: characterization of a susceptibility locus on chromosome 4 and its relation with obesity
Creators Name:	Plum, L., Kluge, R., Giesen, K., Altmüller, J., Ortlepp, J.R. and Joost, H.G.
Abstract:	A backcross model of New Zealand obese mice (NZO) with the lean, atherosclerosis-resistant SJL strain was established to locate genes responsible for obesity, insulin resistance, and type 2 diabetes-like hyperglycemia. In male NZO x F1 backcross mice, a major susceptibility locus for the development of hyperglycemia and hypoinsulinemia (Nidd/SJL) was identified on chromosome 4 between the markers D4Mit278 and D4Mit232, 10-28 cM distal of the previously described Nidd1 locus. The diabetogenic allele has presumably been contributed by the SJL genome, and it appeared to be responsible for approximately 60% of the total prevalence of hyperglycemia. The presence of Nidd/SJL did not alter body weight or weight gain by week 12. Thereafter, it was associated with reduced weight gain or weight loss, presumably as a consequence of decompensated hyperglycemia. In all male backcross mice, the prevalence of hyperglycemia at week 22 increased with the body weight at week 12, suggesting that the development of hyperglycemia was dependent on the degree of obesity. In the absence of Nidd/SJL, mice weighing <50 g at week 12 did not develop hyperglycemia by week 22. In contrast, in animals carrying the diabetogenic allele, the prevalence of hyperglycemia was 20 and 64% when the 12-week weight was <45 and 45-50 g, respectively. These data are consistent with the conclusion that Nidd/SJL represents a diabetes gene that lowers the obesity threshold for the development of hyperglycemia and hypoinsulinemia.
Keywords:	Blood Glucose, Body Mass Index, Body Weight, Cholesterol, Chromosome Mapping, Genetic Crosses, Diabetes Mellitus, Type 2 Diabetes Mellitus, Genetic Predisposition to Disease, Hyperglycemia, Insulin, Inbred Strains Mice, Mutant Strains Mice, Obesity, Triglycerides / Blood, Animals, Mice
Source:	Diabetes
ISSN:	0012-1797
Publisher:	American Diabetes Association
Volume:	49
Number:	9
Page Range:	1590-6
Date:	1 September 2000
Official Publication:	https://doi.org/10.2337/diabetes.49.9.1590
PubMed:	View item in PubMed

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