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 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.
Kim
J H
JH
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Sen
S
S
Avery
C S
CS
Simpson
E
E
Chandler
P
P
Nishina
P M
PM
Churchill
G A
GA
Naggert
J K
JK
D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D016678:Genome; D006943:Hyperglycemia / Q000235:genetics; D006949:Hyperlipidemias / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009765:Obesity / Q000235:genetics; D019655:Quantitative Trait, Heritable