Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine.

Abstract:

: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.

journal_name

J Lipid Res

authors

Wong WP,Altemus JB,Hester JF,Chan ER,Côté JF,Serre D,Sehayek E

doi

10.1194/jlr.M034579

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

816-22

issue

3

eissn

0022-2275

issn

1539-7262

pii

jlr.M034579

journal_volume

54

pub_type

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