Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine |
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Authors: | Winifred P S Wong Jessica B Altemus James F Hester Ernest R Chan Jean-Fran?ois C?té David Serre Ephraim Sehayek |
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Institution: | *Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH;†Institut de Recherches Cliniques de Montreal, Montreal, Canada |
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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. |
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Keywords: | genetics RNA-Seq Gulo Dock5 |
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