Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine[S]

Journal of Lipid Research

James F. Hester¹  David Serre¹  Winifred P.S. Wong¹  Ernest R. Chan¹  Jessica B. Altemus¹  Jean-François Côté²  Ephraim Sehayek³ 

[1] Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH;Institut de Recherches Cliniques de Montreal, Montreal, Canada;To whom correspondence should be addressed. e-mail: [e-mail].;

关键词: genetics;    RNA-Seq;    Gulo;    Dock5;   

DOI  :  

来源: DOAJ

【 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.

【 授权许可】

Unknown