Ninety-seven informative loci were genotyped in a population of 147 (C57BL/6J x KK-Ay)F2 animals of Ay/a genotype to identify QTLs for glucosuria. A population of a/a F2 animals was also examined. Males from parental strain KK-Ay exhibit significant susceptibility to glucosuria (80% incidence at 40 days of age) compared to C57BL/6J. Experimental animals were tested for glucosuria at 40-, 50-, and 60-days of age.
Significant linkage to glucosuria at 40 days mapped to mid-chromosome 6 (29 cM) near D6Mit123 (LOD=6) in the Ay F2 population. This locus explains 32% of the phenotypic variance and is named Guq1 (glucosuria QTL 1). KK-derived alleles at Guq1 confer increased glucosuria severity. This locus also shows suggestive linkage to glucosuria at50 days (LOD=2) and glucosuria at 60 days (LOD=2). Guq1 also displays linkage to glucose tolerance in a/a F2 animals. Since the fasting glucose QTL Fglu (16 cM) maps to this region, Guq1 and Fglu may represent the same locus. Potential candidate genes forGuq1 include Pparg (52.7 cM), Hrh1(49 cM), Npy (26 cM), Crhr2 (28 cM), and Gfpt1 (35.5 cM). Previously identified QTLs overlapping with Guq1 include Obq13 (26.8 cM), Nidd3n (35.5 cM), Dbm1, Adip2 (46.3 cM), Obwq3 (42 cM), Tabw2, and Obq14 (43.5 cM).
A second locus for glucosuria at 40 days in Ay F2 mice named Guq2 (glucosuria QTL 2) mapped to 21.5 cM on mouse Chromosome 16 near D16Mit57 (LOD=3.3). This locus explains 20% of the phenotypic variance. C57BL/6J-derived alleles at Guq2 confer increased glucosuria severity.
Suggestive linkage to glucosuria at 40 days mapped to mouse Chromosome 4 between D4Mit166 (44.5 cM, LOD=2.3) and D4Mit234 (71 cM, LOD=3.8).
Significantlinkage to body weight mapped to mouse Chromosome 16 near D16Mit131 (4.3 cM) and D16Mit136 (28 cM) in the Ay/a F2 population. This locus is named Bwq10 (body weight QTL 10). The LOD scores for body weight at 40-, 50-, and 60-days of age are 3.6, 3.5, and2.1, respectively. C57BL/6J-derived alleles at Bwq10 confer increased body weight. Bwq10 (95% CI interval = 23 cM - 48 cM) and Guq2 (95% confidence interval = 19 cM - 37 cM) overlap and may represent the same locus.
Bwq1 (4.3 cM on chr4) and Bwq2 (35cMon chr6) were also detected in this study. These loci show significant linkage tobody weight at all time points in Ay/a F2 animals. For Bwq1, LOD scores body weight at 40-, 50-, and 60-days of age are 6.1, 5.9, and 5.9, respectively. For Bwq2, LOD scores for body weight at 40-, 50-, and 60-days of age are 5.4, 5.5, and 7.6, respectively.