Calpain-10 is a component of the obesity-related quantitative trait locus Adip1.
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.
Cheverud
James M
JM
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA. cheverud@pcg.wustl.edu
Fawcett
Gloria L
GL
Jarvis
Joseph P
JP
Norgard
Elizabeth A
EA
Pavlicev
Mihaela
M
Pletscher
L Susan
LS
Polonsky
Kenneth S
KS
Ye
Honggang
H
Bell
Graeme I
GI
Semenkovich
Clay F
CF
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
D002154:Calpain; C415197:calpain 10
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