91 female animals from a (C57BL/6J x KK-Ay)F2 intercross were screened for 97 microsatellite markers at an average spacing of 16.5 cM to identify QTLs associated with hyperglycemia, glucose tolerance, and fasting plasma insulin. Parental strain KK-Ayexhibits non-insulin dependent diabetes mellitus (NIDDM) with mild obesity compared to the normoglycemic lean parental strain C57BL/6J.
A QTL associated with glucose intolerance, Giq1, mapped to 21 cM on mouse Chromosome 8 with LOD=5.6 at D8Mit191. Giq1shows a strong effect in the late phase of the intraperitoneal glucose tolerance test (IPGTT) and explains approximately 24.5% of the phenotypic variance. KK-derived alleles confer increased glucose concentration at 120 minutes of the IPGTT. Candidate genes mapping near Giq1 include Npy5r, Cpe, Lpl, and Ucp1. The Giq1 locus is sytenic to human chromosome 3p22-p21.3 or 8p22-p21.3.
Suggestive linkages were also detected at 100 cM on mouse Chromosome 1 with LOD=3.6 at D1Mit150 for fasting glucose levels (Fglu2), at 44.5 cM on mouse Chromosome 4 with LOD=2.9 at D4Mit166 for glucose intolerance (Gauc), and at 71.8 cM on mouse Chromosome 3 with LOD=3.9 at D3Mit84 for fasting plasma insulin (Fpli). The KK-derived allele confers increased glucose concentrationsat D1Mit150 and D4Mit166 loci whereas the C57BL/6J-derived allele confers increased plasma insulin levels at D3Mit84.