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Deficiency of the intermediate filament syemin causes abnormalities in striated muscle and reduces bone mass
Author(s) -
GarciaPelagio Karla P.,
Moorer Megan,
Buo Atum,
Chen Ling,
Stain Joseph,
Bloch Robert
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1036.16
Subject(s) - skeletal muscle , muscle hypertrophy , cardiac muscle , osteopenia , biology , myocyte , myofilament , phenotype , anatomy , medicine , microbiology and biotechnology , endocrinology , osteoporosis , bone mineral , gene , genetics
A large number of diseases ranging from skin disorders, to premature aging, to skeletal and cardiac myopathies are usually associated to mutations in genes encoding intermediate filament (IF) proteins, but synemin presence and function has not been described in skeletal tissue. IFs associate with the contractile machinery and costameres of striated muscle and with intercalated disks in the heart. It also acts as an A‐kinase anchoring protein (AKAP). We study the role of synemin in skeletal and cardiac muscle, and in bone by examining adult mice null for synemin (synm −/−). Our major finding in synm −/− mice are that: 1) Cardiac muscle shows left ventricular remodeling, contractile dysfunction and hypertrophy suggesting a mixed cardiomyopathy. 2) They present a mild skeletal muscle phenotype, a reduction in tension consistent with an increase in sarcolemmal deformability; and the organization of proteins associated with the contractile apparatus and costameres is not significantly altered and, 3) The presence of osteopenia including more than a 2‐fold reduction in trabecular bone and a reduction in cross sectional area. In total, these data suggest an important role for synemin in striated muscle and bone physiology. Support or Funding Information Supported partially by APS‐Physiological Genomics Fellowship and UNAM‐PAPIIT (IA209016) to KPGP; NIH to JPS (R01‐AR063631), and RJB (R01 AR 055928); to NIA to AMB (F31‐AR064673)