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

TitleCalpain-10 is a component of the obesity-related quantitative trait locus Adip1.
Publication TypeJournal Article
Year of Publication2010
AuthorsCheverud, JM, Fawcett, GL, Jarvis, JP, Norgard, EA, Pavlicev, M, L Pletscher, S, Polonsky, KS, Ye, H, Bell, GI, Semenkovich, CF
JournalJ Lipid Res
Volume51
Issue5
Pagination907-13
Date Published2010 May
ISSN1539-7262
KeywordsAlleles, Animals, Calpain, Female, Gene Knockout Techniques, Genetic Complementation Test, Genetic Variation, Hybridization, Genetic, Male, Mice, Obesity, Quantitative Trait Loci
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 F(1) 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.

DOI10.1194/jlr.M900128
Alternate JournalJ. Lipid Res.
PubMed ID20388922
PubMed Central IDPMC2853458
Grant ListDK-76729 / DK / NIDDK NIH HHS / United States
DK-55736 / DK / NIDDK NIH HHS / United States
R37 DK031842 / DK / NIDDK NIH HHS / United States
DK-31842 / DK / NIDDK NIH HHS / United States
DK-20579 / DK / NIDDK NIH HHS / United States
DK-20595 / DK / NIDDK NIH HHS / United States
P30 DK056341 / DK / NIDDK NIH HHS / United States
K23 DK073451 / DK / NIDDK NIH HHS / United States
R01 DK076729 / DK / NIDDK NIH HHS / United States
DK-73451 / DK / NIDDK NIH HHS / United States
P60 DK020579 / DK / NIDDK NIH HHS / United States
R01 DK055736 / DK / NIDDK NIH HHS / United States
P30 DK020579 / DK / NIDDK NIH HHS / United States
R01 DK031842 / DK / NIDDK NIH HHS / United States
DK-56341 / DK / NIDDK NIH HHS / United States
R56 DK055736 / DK / NIDDK NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States
P60 DK020595 / DK / NIDDK NIH HHS / United States