title: Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity.
abstract: The TallyHo (TH) mouse strain is a polygenic model for Type 2 diabetes with obesity. Genetic analysis in backcross progeny from a cross between F1 [C57BL/6J (B6) x TH] and TH mice mapped a quantitative trait locus (QTL) named TH-associated body weight 2 (tabw2) to chromosome 6. The TH-derived allele is associated with increased body weight. As a first step to identify the molecular basis of this obesity QTL, we constructed a congenic line of mice on the B6 genetic background that carries a genomic region from TH mice containing tabw2. Congenic mice homozygous for tabw2 (B6.TH-tabw2/tabw2) fed a chow diet exhibited slightly, but significantly, higher body weight and body fat and plasma leptin levels compared with controls (B6.TH-+/+). This difference was exacerbated when the animals were maintained on a high-fat and high-sucrose (HFS) diet. The diet-induced obesity in tabw2 congenic mice is accompanied by hyperleptinemia, mild hyperinsulinemia, impaired glucose tolerance, and reduced glucose uptake in adipose tissue in response to insulin administration. Using F2 progeny fed a HFS diet from an intercross of B6.TH-tabw2/+ mice, we were able to refine the map position of the tabw2 obesity susceptibility locus to a 15-cM region (95% confidence interval) extending distally from the marker D6Mit102. In summary, tabw2 congenic mice are a new animal model for diet-induced obesity that will be valuable for the study of gene-diet interactions.
authors.affiliation: Department of Nutrition, The University of Tennessee, Knoxville 37996-1920, USA. jhkim@utk.edu
authors.forename: Jung Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Taryn P
authors.initials: TP
authors.lastname: Stewart
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.forename: Hyoung Yon
authors.initials: HY
authors.lastname: Kim
authors.forename: Patsy M
authors.initials: PM
authors.lastname: Nishina
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Naggert
mesh_terms: D000483:Alleles; D000818:Animals; D001835:Body Weight / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003433:Crosses, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006946:Hyperinsulinism / Q000473:pathology; D020738:Leptin / Q000378:metabolism; D008126:Lod Score; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D009765:Obesity / Q000235:genetics*; D020161:Physical Chromosome Mapping
chemical_list: D020738:Leptin; D005947:Glucose