Genetic ablation of caspase‐2 decreases muscle function in female mice

Abstract

Caspase‐2, a cysteine aspartate protease, is an important regulator of apoptosis. We have previously shown that caspase‐2 modulates bone homeostasis. Specifically, we found that 2‐month old female and 5‐month old male Casp2−/− mice exhibited significantly reduced bone mass when compared to wild‐type (WT) mice that continued with aging. Bone is intricately linked to muscle mechanics and function; however, the role of caspase‐2 in skeletal muscle is not clear. This study examined the effect of caspase‐2 on muscle mass and function in 6‐mo‐old WT and Casp2−/− C57BL/6 mice of both sexes. Quantitative nuclear magnetic resonance was used to measure whole‐body lean mass and fat mass. Muscle mass was determined by measuring the mass of quadriceps, gastrocnemius and soleus muscles as well as by measuring cross‐sectional area (CSA) of gastrocnemius muscle. Peak isometric torque of ankle plantarflexors (gastrocnemius, soleus, plantaris) was measured in vivo to determine muscle function. We found decreased body weight and lean mass in both male and female Casp2−/− mice. Muscle mass, CSA and function were not significantly different between male WT and Casp2−/− mice when the data was adjusted for total body lean mass. Similarly, muscle mass and CSA were not different between female Casp2−/− and WT mice. However, significant decrement in muscle function (p < 0.0001) was observed in female Casp2−/− mice compared to female WT mice. We confirmed that our findings in female mice were independent of caspase‐2’s effects on sensorimotor function as there was no difference in sciatic or sural nerve conduction velocity between WT and Casp2−/− mice. Together, these findings suggest a gender‐specific role for caspase‐2 in modulating skeletal muscle function.Support or Funding InformationOwens Foundation