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

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 t he diabetes syndrome has been carried out using male backcross 1 progeny ob tained 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 (Q TLs), Tanidd1-3 (TH-associated NIDDM) linked to hyperglycemia. The major QT L (common in both crosses), Tanidd1, maps to chromosome (Chr) 19. Additiona lly, gene-gene interactions contributing to hyperglycemia have been observe d between Tanidd1 and a locus on Chr 18 as well as between Tanidd2 and a lo cus 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 in teracts with additional genes to lead to an observable phenotype. (C) 2001 Academic Press.