GROWTH AND MUSCLE DEFECTS IN MICE LACKING ADULT MYOSIN HEAVY-CHAIN GENES

The three adult fast myosin heavy chains (MyHCs) constitute the vast m ajority of the myosin in adult skeletal musculature, and are >92% iden tical. We describe mice carrying null mutations in each of two predomi nant adult fast MyHC genes, IIb and IId/x. Both null strains exhibit g rowth and muscle defects, but the defects are different between the tw o strains and do not correlate with the abundance or distribution of e ach gene product. For example, despite the fact that MyHC-IIb accounts for >70% of the myosin in skeletal muscle and shows the broadest dist ribution of expression, the phenotypes of IIb null mutants are general ly milder than in the MyHC-IId/x null strain. In addition, in a muscle which expresses both IIb and IId/x MyHC in wild-type mice, the histol ogical defects are completely different for null expression of the two genes. Most striking is that while both null strains exhibit physiolo gical defects in isolated muscles, the defects are distinct. Muscle fr om IIb null mice has significantly reduced ability to generate force w hile IId null mouse muscle generates normal amounts of force, but has altered kinetic properties. Many of the phenotypes demonstrated by the se mice are typical in human muscle disease and should provide insight into their etiology.