Mutation of the IIB myosin heavy chain gene results in muscle fiber loss and compensatory hypertrophy

The fast skeletal IIb gene is the source of most myosin heavy chain (MyHC) in adult mouse skeletal muscle. We have examined the effects of a null muta tion in the IIb MyHC gene on the growth and morphology of mouse skeletal mu scle. Loss in muscle mass of several head and hindlimb muscles correlated w ith amounts of IIb MyHC expressed in that muscle in wild types. Decreased m ass was accompanied by decreases in mean fiber number, and immunological an d ultrastructural studies revealed fiber pathology. However, mean cross-sec tional area was increased in all fiber types, suggesting compensatory hyper trophy. Loss of muscle and body mass was not attributable to impaired chewi ng, and decreased food intake as a softer diet did not prevent the decrease in body mass. Thus loss of the major MyHC isoform produces fiber loss and fiber pathology reminiscent of muscle disease.