SPEG-deficient skeletal muscles exhibit abnormal triad and defective calcium handling

Human Molecular Genetics
Virginia HuntoonPankaj B Agrawal

Abstract

Centronuclear myopathies (CNM) are a subtype of congenital myopathies (CM) characterized by skeletal muscle weakness and an increase in the number of central myonuclei. We have previously identified three CNM probands, two with associated dilated cardiomyopathy, carrying striated preferentially expressed gene (SPEG) mutations. Currently, the role of SPEG in skeletal muscle function is unclear as constitutive SPEG-deficient mice developed severe dilated cardiomyopathy and died in utero. We have generated a conditional Speg-KO mouse model and excised Speg by crosses with striated muscle-specific cre-expressing mice (MCK-Cre). The resulting litters had a delay in Speg excision consistent with cre expression starting in early postnatal life and, therefore, an extended lifespan up to a few months. KO mice were significantly smaller and weaker than their littermate-matched controls. Histopathological skeletal muscle analysis revealed smaller myofibers, marked fiber-size variability, and poor integrity and low number of triads. Further, SPEG-deficient muscle fibers were weaker by physiological and in vitro studies and exhibited abnormal Ca2+ handling and excitation-contraction (E-C) coupling. Overall, SPEG deficiency in skeletal muscl...Continue Reading

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Citations

Oct 19, 2019·Journal of Clinical Laboratory Analysis·Jia TangLiangping Luo
Oct 18, 2020·Cardiovascular Research·Hannah CampbellXander H T Wehrens
Dec 24, 2020·Human Molecular Genetics·Shiyu LuoPankaj B Agrawal
Jun 3, 2021·International Journal of Molecular Sciences·Shiyu LuoPankaj B Agrawal

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