Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine.
J Lipid Res
; 54(3): 816-822, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23248330
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Catepsina B
/
Colesterol
/
Mucosa Intestinal
Limite:
Animals
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2013
Tipo de documento:
Article