Xin-deficient mice display myopathy, impaired contractility, attenuated muscle repair and altered satellite cell functionality Academic Article uri icon

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abstract

  • 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 SCs, we studied SCs 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 SCs 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 SCs did not translate to more proliferating myoblasts, we investigated whether Xin-/- SCs displayed an exaggerated loss by apoptosis. More apoptotic SCs (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.

authors

  • Al-Sajee, D
  • Nissar, AA
  • Coleman, SK
  • Rebalka, IA
  • Chiang, A
  • Wathra, R
  • van der Ven, PFM
  • Orfanos, Z
  • Hawke, Thomas

publication date

  • June 2015