MYOSIN HEAVY-CHAINS IIA AND IID ARE FUNCTIONALLY DISTINCT IN THE MOUSE

Myosin in adult murine skeletal muscle is composed primarily of three adult fast myosin heavy chain (MyHC) isoforms. These isoforms, MyHC-II a, -IId, and -IIb, are >93% identical at the amino acid level and are broadly expressed in numerous muscles, and their genes are tightly lin ked. Mice with a null mutation in the MyHC-IId gene have phenotypes th at include growth inhibition, muscle weakness, histological abnormalit ies, kyphosis (spinal curvature), and aberrant kinetics of muscle cont raction and relaxation. Despite the lack of MyHC-IId, IId null mice ha ve normal amounts of myosin in their muscles because of compensation b y the MyHC-IIa gene. In each muscle examined from IId null mice, there was an increase in MyHC-IIa-containing fibers. MyHC-IIb content was u naffected in all muscles except the masseter, where its expression was extinguished in the IId null mice. Cross-sectional fiber areas, total muscle cross-sectional area, and total fiber number were affected in ways particular to each muscle. Developmental expression of adult MyHC genes remained unchanged in IId null mice. Despite this universal com pensation of MyHC-IIa expression, IId null mice have severe phenotypes . We conclude that despite the similarity in sequence, MyHC-IIa and -I Id have unique roles in the development and function of skeletal muscl e.