Coincidence of loci for glucosuria and obesity in type 2 diabetes-prone KK-Ay mice.

BACKGROUND

Colleagues and I previously performed a quantitative trait locus (QTL) analysis on non-insulin-dependent diabetes mellitus (NIDDM) traits (hyperglycemia and glucose intolerance) and body weight (obesity) in KK-Ay mice. QTLs for NIDDM traits were quite different from those for body weight. In this study, I performed a QTL analysis on glucosuria to characterize its genetics and pathophysiology in KK-Ay mice.

MATERIAL/METHODS: Onset and severity of glucosuria were examined at 40 days (UR40), 50 days (UR50), and 60 days (UR60) after birth, and I compared the results with those for NIDDM traits and body weight.

RESULTS

Suggestive QTLs were identified on chromosomes 4 (UR60) and 6 (UR60). Significant QTLs were identified on chromosomes 6 (UR40 and UR50, Guq1), and 16 (UR40, Guq2). At the locus on chromosome 4 and Guq1, the KK allele was associated with increases in glucosuria severity and body weight; on the contrary, the KK allele was associated with decreases in glucosuria severity and body weight at Guq2. With regard to the fasting plasma glucose levels at autopsy, the KK allele at the Guq1 locus was significantly associated with elevated glucose levels, and there was a trend that the KK allele at Guq2 was associated with decreased glucose levels.

CONCLUSIONS

Glucosuria is a complex trait that has a strong relationship to body weight rather than to NIDDM traits. A genetic relationship among glucosuria, body weight, and fasting glucose levels was confirmed. Allelism between glucosuria QTL and body weight QTL was strongly suggested.