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  • Hidden disease susceptibility and sexual dimorphism in the heterozygous knockout of Cyp51 from cholesterol synthesis [Elektronski vir]
    Lewinska, Monika ...
    We examined the genotype-phenotype interactions of Cyp51+/- mice carrying one functional allele of lanosterol 14alpha-demethylase from cholesterol biosynthesis. No distinct developmental or ... morphological abnormalities were observed by routine visual inspection of Cyp51+/- and Cyp51+/+ mice and fertility was similar. We further collected a large data-set from female and male Cyp51+/- mice and controls fed for 16 weeks with three diets and applied linear regression modeling. We used 3 predictor variables (genotype, sex, diet), and 39 response variables corresponding to the organ characteristics (7), plasma parameters (7), and hepatic gene expression (25). We observed significant differences between Cyp51+/- and wild-type mice in organ characteristics and blood lipid profile. Hepatomegaly was observed in Cyp51+/- males, together with elevated total and low-density lipoprotein cholesterol. Cyp51+/- females fed high-fat, high-cholesterol diet were leaner and had elevated plasma corticosterone compared to controls. We observed elevated hepatocyte apoptosis, mitosis and lipid infiltration in heterozygous knockouts of both sexes. The Cyp51+/- females had a modified lipid storage homeostasis protecting them from weight-gain when fed high-fat high-cholesterol diet. Malfunction of one Cyp51 allele therefore initiates disease pathways towards cholesterol-linked liver pathologies and sex-dependent response to dietary challenge.
    Source: PloS one [Elektronski vir]. - ISSN 1932-6203 (Vol. 9, iss. 11, Nov. 2014)
    Type of material - e-article
    Publish date - 2014
    Language - english
    COBISS.SI-ID - 31705049

    Link(s):

    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0112787
    DOI

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