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Characterization of Nob3, a major quantitative trait locus for obesity and hyperglycemia on mouse chromosome 1

Item Type:Article
Title:Characterization of Nob3, a major quantitative trait locus for obesity and hyperglycemia on mouse chromosome 1
Creators Name:Vogel, H. and Nestler, M. and Rueschendorf, F. and Block, M.D. and Tischer, S. and Kluge, R. and Schurmann, A. and Joost, H.G. and Scherneck, S.
Abstract:New Zealand obese (NZO) mice present a metabolic syndrome of obesity, insulin resistance, and diabetes. In order to identify chromosomal segments associated with these traits, we intercrossed NZO mice with the lean and diabetes-resistant C57BL/6J (B6) strain. Obesity and hyperglycaemia in the (NZOxB6)F2 intercross population were predominantly due to a broad QTL on Chromosome 1 (Nob3; LOD score 16.1, 16.0, 4.0 for body weight, body fat, and blood glucose, respectively), producing a difference between genotypes of 12.7 or 5.2 g of body weight and 12.0 or 4.0 g of body fat in females or males, respectively. In addition, significant QTL on Chromosomes 3 and 13, suggestive QTL on Chromosomes 4, 6, 9, 12, 14, and 19 contributed to the obese phenotype. Distal Chromosome 5 was significantly linked with plasma cholesterol (LOD score 10.7). Introgression of two segments of Nob3 into B6 confirmed the adipogenic effect of the QTL and suggested the presence of at least one causal gene. Haplotype mapping reduced the critical region of the distal part of the QTL to 31 Mbp containing the potential candidates Nr1i3, Apoa2, Atp1a2, Prox1, and Hsd11b1. We conclude that obesity and hyperglycaemia of NZO is to a large part caused by variant genes located in Nob3 on Chromosome 1. Since these exert robust effects on a B6 background, the QTL Nob3 is a prime target for identification of a novel diabesity gene. Key words: positional cloning, metabolic syndrome, diabetes, cholesterol.
Keywords:Positional Cloning, Metabolic Syndrome, Diabetes, Cholesterol, New Zealand Obese Mouse, Animals, Mice
Source:Physiological Genomics
Publisher:American Physiological Society
Page Range:226-232
Date:9 July 2009
Official Publication:https://doi.org/10.1152/physiolgenomics.00011.2009
PubMed:View item in PubMed

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