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Timeline of cardiac dystrophy in 3–18-month-old MDX mice

Authors

  • Christel Van Erp PhD,

    1. Centre for Systems Biology, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia 4350
    Current affiliation:
    1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
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    • The first two authors contributed equally to this work.

  • David Loch PhD,

    1. Centre for Systems Biology, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia 4350
    Current affiliation:
    1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
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    • The first two authors contributed equally to this work.

  • Nicola Laws PhD,

    1. Centre for Systems Biology, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia 4350
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  • Andrea Trebbin BAppl Sc,

    1. Centre for Systems Biology, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia 4350
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  • Andrew J. Hoey PhD

    Corresponding author
    1. Centre for Systems Biology, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia 4350
    • Centre for Systems Biology, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia 4350
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Abstract

The dystrophin-deficient (mdx) mouse remains the most commonly used model for Duchenne muscular dystrophy (DMD). Mdx mice show a predominantly covert cardiomyopathy, the hallmark of which is fibrosis. We compared mdx and normal mice at six ages (3, 6, 9, 12, 15, and 18 months) using in vivo assessment of cardiac function, selective collagen staining, and measures of TGF-β mRNA, Evans blue dye infiltration, macrophage infiltration, and aortic wall thickness. Clear temporal progression was demonstrated, including early fragility of cardiomyocyte membranes, which has an unrelated impact on cardiac function but is associated with macrophage infiltration and fibrosis. Aortic wall thickness is less in older mdx mice. Mdx mice display impaired responses to inotropic challenge from a young age; this is indicative of altered adrenoreceptor function. We draw attention to the paradox of ongoing fibrosis in mdx hearts without a strong molecular signature (in the form of TGF-β mRNA expression). Muscle Nerve, 2010

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