A20 Assessment of muscle regeneration in the R6/2 mouse model of huntington’s disease

Background Skeletal muscle atrophy is one of the hallmarks of Huntington’s disease (HD), and it correlates with inflammation, mitochondrial dysfunction, and altered energy metabolism. Although improvement in muscle wasting has been shown to slow disease progression and increase life span in animal models, the precise mechanism of overall muscle wasting is not well studied. Aim Using an acute injury model, we aimed to investigate the effects of mutant HTT expression on satellite cell regeneration capacity in the R6/2 mouse model. Methods We used adult and neonatal R6/2 mice and their WT littermates. A chemical injury model was employed using cardiotoxin (CTX) in the tibialis anterior muscle. To assess tissue remodeling, we performed immunohistochemistry using laminin to stain basement membrane and embryonic myosin heavy chain (eMHC) as an indicator of muscle regeneration at 4 weeks and 1 week of post-CTX injection, respectively. Results Body weight and fiber diameter were significantly reduced in both adult and neonatal R6/2 mice compared to WT littermates. At four weeks post-injection, fiber diameter was the same between saline and CTX injected group in WT mice. Yet, fiber diameter was increased in the R6/2 CTX compared to the R6/2 saline group. We found a trend towards increased eMHC positive cells in R6/2 compared to the WT littermates at 1-week post-injection. Conclusion R6/2 skeletal muscle has the ability to regenerate new fibers following an acute injury, and the regeneration process was not profoundly affected by mutant huntingtin expression. We will further investigate HD satellite cell proliferation capacity (i.e., Pax7 positive cells) and inflammatory response (i.e., CD68, CD11b) in response to acute muscle injury.