Isoform Transitions of the Myosin Binding Protein C Family in Developing Human and Mouse Muscles

Lack of Isoform Transcomplementation in Cardiac Muscle

From the CNR Center of Muscle Biology & Physiopathology (A.C., S.S.), Department of Biomedical Sciences, University of Padova (Italy); the European Molecular Biology Laboratory (M.G.), Heidelberg, Germany; and the Department of Cell Biology (D.O.F.), University of Potsdam, (Germany).

Correspondence to Dr Mathias Gautel, European Molecular Biology Laboratory, Meierhofstr. 1, 69117 Heidelberg, Germany. E-mail Gautel{at}EMBL-Heidelberg.de

Abstract—Mutations in the gene for the cardiac isoform of myosin binding protein C (MyBP-C) have been identified as the cause of chromosome 11–associated autosomal-dominant familial hypertrophic cardiomyopathy (FHC). Most mutations produce a truncated polypeptide that lacks the sarcomeric binding region. We have now investigated the expression pattern of the cardiac and skeletal isoforms of cMyBP-C in mice and humans by in situ hybridization and immunofluorescence microscopy using specific antibodies and probes. We demonstrate that the cardiac isoform is expressed only in cardiac muscle throughout development. The slow and fast isoforms of MyBP-C remain specific for skeletal muscle, where they can be coexpressed. Immunological evidence also suggests that an embryonic isoform of MyBP-C precedes the expression of slow MyBP-C in developing skeletal muscle. This suggests that transcomplementation of MyBP-C isoforms is possible in skeletal but not cardiac muscle.

Key Words: familial hypertrophic cardiomyopathy • myosin binding protein C • C-protein isoforms • embryonic expression patterns • cardiac muscle

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