Title

Genetic analysis of a new mouse model for non-insulin-dependent diabetes.

Document Type

Article

Publication Date

2001

Keywords

Chromosome-Mapping, Crosses-Genetic, Diabetes-Mellitus-Non-Insulin-Dependent, Disease-Models-Animal, Female, Genetic-Predisposition-to-Disease, Genome, Hyperglycemia, Hyperlipidemia, Male, Mice, Mice-Inbred-C57BL, Mice-Inbred-Strains, Obesity, Quantitative-Trait, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

JAX Source

Genomics 2001 Jun; 74(3):273-86.

Grant

CA34196/CA/NCI, DK46977/DK/NIDDK

Abstract

The TallyHo (TH) mouse strain is a newly established model for non-insulin-dependent diabetes mellitus (NIDDM). TH mice show obesity, hyperinsulinemia, hyperlipidemia, and male-limited hyperglycemia. A genetic dissection of the diabetes syndrome has been carried out using male backcross 1 progeny obtained from crosses between (C57BL/6J x TH)F1 and TH mice or (CAST/Ei x TH)F1 and TH mice. A genome-wide scan reveals three quantitative trait loci (QTLs), Tanidd1-3 (TH-associated NIDDM) linked to hyperglycemia. The major QTL (common in both crosses), Tanidd1, maps to chromosome (Chr) 19. Additionally, gene-gene interactions contributing to hyperglycemia have been observed between Tanidd1 and a locus on Chr 18 as well as between Tanidd2 and a locus on Chr 16. The overt hyperglycemia in TH mice is, therefore, likely due to a mutation in a major diabetes susceptibility locus on Chr 19, which interacts with additional genes to lead to an observable phenotype. Copyright 2001 Academic Press.