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  • 标题:Calpain-10 is a component of the obesity-related quantitative trait locus Adip1
  • 本地全文:下载
  • 作者:James M. Cheverud ; Gloria L. Fawcett ; Joseph P. Jarvis
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2010
  • 卷号:51
  • 期号:5
  • 页码:907-913
  • DOI:10.1194/jlr.M900128-JLR200
  • 语种:English
  • 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.
  • 关键词:diabetes ; glucose tolerance ; leptin ; quantitative hybrid complementation test
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