出版社：American Society for Biochemistry and Molecular Biology
摘要：We previously mapped Adip1 , an obesity quantitative trait locus (QTL), to the central portion of murine chromosome 1 containing the calpain-10 ( Capn10 ) gene. Human studies have associated calpain-10 ( CAPN10 ) variants with type 2 diabetes and various metabolic traits. We performed a quantitative hybrid complementation test (QHCT) to determine whether differences attributed to Adip1 are the result of variant Capn10 alleles in LG/J and SM/J mice. We crossed LG/J and SM/J to wild-type (C57BL/6J) and Capn10 knockout ( Capn10 −/−) mice to form four F1 hybrid groups: LG/J by wild-type, LG/J by Capn10 −/−, SM/J by wild-type, and SM/J by Capn10 −/−. We performed a two-way ANOVA with the experimental strain, tester strain, and their interaction as the factors. Significant interaction indicates a quantitative failure to complement. We found failure to complement for fat, organ, and body weights, and leptin, female free fatty acid, and triglyceride levels. Capn10 −/− resulted in heavier weights and higher serum levels in LG/J crosses but not in SM/J crosses. For glucose tolerance and insulin response tests, the Capn10 −/− allele resulted in lower glucose levels in crosses with SM/J but had no effect in the LG/J crosses. Differences between the LG/J and SM/J Capn10 alleles are the likely source of some of the QTL effects mapped to Adip1 in the LG/J–by–SM/J cross. Capn10 plays an important role in regulating obesity and diabetes in mice.
