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Xin‐deficient mice display myopathy, impaired contractility, attenuated muscle repair and altered satellite cell functionality
Author(s) -
AlSajee D.,
Nissar A. A.,
Coleman S. K.,
Rebalka I. A.,
Chiang A.,
Wathra R.,
Ven P. F. M.,
Orfanos Z.,
Hawke T. J.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12455
Subject(s) - cardiotoxin , skeletal muscle , myod , myocyte , medicine , regeneration (biology) , myopathy , myogenesis , endocrinology , contractility , population , desmin , tunel assay , apoptosis , biology , chemistry , microbiology and biotechnology , immunohistochemistry , biochemistry , vimentin , environmental health
Aim Xin is an F‐actin‐binding protein expressed during development of cardiac and skeletal muscle. We used Xin‐/‐ mice to determine the impact of Xin deficiency on different aspects of skeletal muscle health, including functionality and regeneration. Methods Xin‐/‐ skeletal muscles and their satellite cell ( SC ) population were investigated for the presence of myopathic changes by a series of histological and immunofluorescent stains on resting uninjured muscles. To further understand the effect of Xin loss on muscle health and its SC s, we studied SC s responses following cardiotoxin‐induced muscle injury. Functional data were determined using in situ muscle stimulation protocol. Results Compared to age‐matched wild‐type ( WT ), Xin‐/‐ muscles exhibited generalized myopathy and increased fatigability with a significantly decreased force recovery post‐fatiguing contractions. Muscle regeneration was attenuated in Xin‐/‐ mice. This impaired regeneration prompted an investigation into SC content and functionality. Although SC content was not different, significantly more activated SC s were present in Xin‐/‐ vs. WT muscles. Primary Xin‐/‐ myoblasts displayed significant reductions (approx. 50%) in proliferative capacity vs. WT ; a finding corroborated by significantly decreased MyoD‐positive nuclei in 3 days post‐injury Xin‐/‐ muscle vs. WT . As more activated SC s did not translate to more proliferating myoblasts, we investigated whether Xin‐/‐ SC s displayed an exaggerated loss by apoptosis. More apoptotic SC s ( TUNEL +/Pax7+) were present in Xin‐/‐ muscle vs. WT . Furthermore, more Xin‐/‐ myoblasts were expressing nuclear caspase‐3 compared to WT at 3 days post‐injury. Conclusion Xin deficiency leads to a myopathic condition characterized by increased muscle fatigability, impaired regeneration and SC dysfunction.