title: Calpain-10 is a component of the obesity-related quantitative trait locus Adip1.
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.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA. cheverud@pcg.wustl.edu
authors.forename: James M
authors.initials: JM
authors.lastname: Cheverud
authors.forename: Gloria L
authors.initials: GL
authors.lastname: Fawcett
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Jarvis
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Norgard
authors.forename: Mihaela
authors.initials: M
authors.lastname: Pavlicev
authors.forename: L Susan
authors.initials: LS
authors.lastname: Pletscher
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Polonsky
authors.forename: Honggang
authors.initials: H
authors.lastname: Ye
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
authors.forename: Clay F
authors.initials: CF
authors.lastname: Semenkovich
mesh_terms: D000483:Alleles; D000818:Animals; D002154:Calpain / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D005260:Female; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D014644:Genetic Variation; D006824:Hybridization, Genetic; D008297:Male; D051379:Mice; D009765:Obesity / Q000235:genetics*; D040641:Quantitative Trait Loci
chemical_list: D002154:Calpain; C415197:calpain 10
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