ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums

Jeannie Chan, Michael C. Mahaney, Rampratap S. Kushwaha, Jane F. VandeBerg, John L. VandeBerg

    Research output: Contribution to journalArticle

    7 Scopus citations

    Abstract

    High-responding opossums are susceptible to developing hypercholesterolemia on a high-cholesterol diet, but low-responding opossums are resistant. The observation of low biliary cholesterol and low biliary phospholipids in high responders suggested that the ABCB4 gene affects response to dietary cholesterol. Two missense mutations (Arg29Gly and Ile235Leu) were found in the ABCB4 gene of high responders. High responders (ATHH strain) were bred with low responders (ATHE or ATHL strain) to produce F1 and F2 progeny in two different genetic crosses (KUSH6 and JCX) to determine the effect of ABCB4 allelic variants on plasma cholesterol concentrations after a dietary challenge. Pedigree-based genetic association analyses consistently implicated a variant in ABCB4 or a closely linked locus as a major, but not the sole, genetic contributor to variation in the plasma cholesterol response to dietary cholesterol. High responders, but not low responders, developed liver injury as indicated by elevated plasma biomarkers of liver function, probably reflecting damage to the canalicular membrane by bile salts because of impaired phospholipid secretion. Our results implicate ABCB4 as a major determinant of diet-induced hypercholesterolemia in high-responding opossums and suggest that other genes inter act with ABCB4 to regulate lipemic response to dietary cholesterol.

    Original languageEnglish (US)
    Pages (from-to)2922-2928
    Number of pages7
    JournalJournal of lipid research
    Volume51
    Issue number10
    DOIs
    StatePublished - Oct 1 2010

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    Keywords

    • Bile
    • Liver disease
    • Monodelphis domestica
    • Phospholipid

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology
    • Cell Biology

    Cite this

    Chan, J., Mahaney, M. C., Kushwaha, R. S., VandeBerg, J. F., & VandeBerg, J. L. (2010). ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums. Journal of lipid research, 51(10), 2922-2928. https://doi.org/10.1194/jlr.M005553