Key result
Xin deficiency in mice drives generalized myopathy and impaired regeneration, reducing myoblast proliferation by ~50%.
Xin deficiency in mice leads to a myopathic condition characterized by increased muscle fatigability, impaired regeneration, and satellite cell dysfunction.
Xin loss impairs murine muscle regeneration; leaves open whether targeting Xin affects human myopathies.
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.
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Al‐Sajee et al. (2015) studied Xin deficiency / skeletal muscle health. Xin deficiency (Xin-/-) vs. Wild-type (WT) mice was evaluated on Myopathy, muscle fatigability, regeneration, and satellite cell functionality. Xin deficiency in mice led to generalized myopathy, increased muscle fatigability, impaired regeneration, and satellite cell dysfunction, including a ~50% reduction in myoblast proliferative capacity.
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