Calpain-10 is a component of the obesity-related quantitative trait locus Adip1

James M. Cheverud, Gloria L. Fawcett, Joseph P. Jarvis, Elizabeth A. Norgard, Mihaela Pavlicev, L. Susan Pletscher, Kenneth S. Polonsky, Honggang Ye, Graeme I. Bell, Clay F. Semenkovich

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)907-913
Number of pages7
JournalJournal of lipid research
Volume51
Issue number5
DOIs
StatePublished - May 1 2010

Keywords

  • Diabetes
  • Glucose tolerance
  • Leptin
  • Quantitative hybrid complementation test

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