Adeno-associated virus-mediated expression of an inactive CaMKII beta mutant enhances muscle mass and strength in mice

A concurrent reduction in muscle mass and strength is frequently observed in numerous conditions, including neuromuscular disease, ageing, and muscle inactivity due to limb immobilization or prolonged bed rest. Thus, identifying the molecular mechanisms that control skeletal muscle mass and strength is fundamental for developing interventions aimed at counteracting muscle loss (muscle atrophy). It was recently reported that muscle atrophy induced by denervation of motor nerves was associated with increased expression of Ca2+/calmodulin-dependent protein serine/threonine kinase II beta (CaMKII beta) in muscle. In addition, treatment with KN-93 phosphate, which inhibits CaMKII-family kinases, partly suppressed denervation-induced muscle atrophy. Therefore, to test a possible role for CaMKII beta in muscle mass regulation, we generated and injected recombinant adeno-associated virus (AAV) vectors encoding wild-type (AAV-WT), inactive (AAV-K43 M), or constitutively active (AAV-T287D) CaMKII beta into the left hindlimb tibialis anterior muscle of mice at three months of age. Although AAV-WT infection induced expression of exogenous CaMKII beta in the hindlimb muscle, no significant changes in muscle mass and strength were observed. By contrast, AAV-K43 M or AAV-T287D infection induced exogenous expression of the corresponding mutants and significantly increased or decreased the muscle mass and strength of the infected hind limb, respectively. Together, these findings demonstrate the potential of CaMKII beta as a novel therapeutic target for enhancing muscle mass and strength. (c) 2021 Elsevier Inc. All rights reserved.