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  • 标题:Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine
  • 本地全文:下载
  • 作者:Winifred P. S. Wong ; Jessica B. Altemus ; James F. Hester
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2013
  • 卷号:54
  • 期号:3
  • 页码:816-822
  • DOI:10.1194/jlr.M034579
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:We used a mouse C57BL/6J×CASA/Rk intercross to map a locus on chromosome 14 that displayed a gender-dependent effect on cholesterol absorption from the intestine. Studies in congenic animals revealed a complex locus with multiple operating genetic determinants resulting in alternating gender-dependent phenotypic effects. Fine-mapping narrowed the locus to a critical 6.3 Mb interval. Female subcongenics, but not males, of the critical interval displayed a decrease of 33% in cholesterol absorption. RNA-Seq analysis of female subcongenic jejunum revealed that cysteine protease cathepsin B (Ctsb) is a candidate to explain the interval effect. Consistent with the phenotype in critical interval subcongenics, female Ctsb knockout mice, but not males, displayed a decrease of 31% in cholesterol absorption. Although studies in Ctsb knockouts revealed a gender-dependent effect on cholesterol absorption, further fine-mapping dismissed a role for Ctsb in determining the effect of the critical 6.3 Mb interval on cholesterol absorption.
  • 关键词:genetics ; RNA-Seq ; Gulo ; Dock5
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