First Author | Wong WP | Year | 2013 |
Journal | J Lipid Res | Volume | 54 |
Issue | 3 | Pages | 816-22 |
PubMed ID | 23248330 | Mgi Jnum | J:194292 |
Mgi Id | MGI:5471909 | Doi | 10.1194/jlr.M034579 |
Citation | Wong WP, et al. (2013) Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine. J Lipid Res 54(3):816-22 |
abstractText | We used a mouse C57BL/6JxCASA/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. |