Experiment
Inbred strain C57BL/6Scl secretes less insulin and exhibits higher blood glucose levels than inbred strain C3H/HeSlc when subject to an intraperitoneal glucose tolerance test (IPGTT). A pooling strategy was used to identify QTLs associated with glucose intolerance in a population of (C3H/HeSlc x C57BL/6Slc)F2 male animals. 30 F2 males with the highest 30-minute glucose values and 30 F2 males with the lowest 30-minute glucose values were typed for 87 polymorphic markers spanning the 19 autosomes. Significant loci were confirmed by screening (using the same set of markers) a population of 59 F3 male animals generated from crossing F2 animals with the highest (high x high) and lowest (low x low) glucose values. A locus on mouse Chromosome 2, Bglu1, is significantly associated with blood glucose levels. Bglu1 gave a LOD score of 8.3 at D2Mit48 and has a QTL range from 65 cM - 105 cM defined by D2Mit62 and D2Mit265. C57BL/6Slc-derived alleles appear to have a dominant effect in increasing blood glucose levelsat Bglu1. Candidate genes in the region of Bglu1 include Chgb, Pcsk2, A (agouti), Kcnb1, and Hnf4a. A second locus associated with blood glucose levels, Bglu2, mapped to mouse Chromosome 13 giving a LOD score of 4.2 at D13Mit148 with a QTL range from 59 cM- 61 cM defined by D13Mit148 and D13Mit76. C57BL/6Slc-derived alleles appear to influence blood glucose levels in a codominant fashion at Bglu2. Candidate genes in the region of Bglu2 include Pcsk1 and Pik3r1. Direct sequencing of Pcsk1 and Pcsk2 did notreveal polymorphisms or mutations in C57BL/6Scl or C3H/HeSlc parental inbred strains.
Analysis Tools