Phenotypes of myopathy-related beta-tropomyosin mutants in human and mouse tissue cultures

Mutations in TPM2 result in a variety of myopathies characterised by variable clinical and morphological features. We used human and mouse cultured cells to study the effects of b-TM mutants. The mutants induced a range of phenotypes in human myoblasts, which generally changed upon differentiation to myotubes. Human myotubes transfected with the E41K-b-TMEGFP mutant showed perinuclear aggregates. The G53ins-b-TMEGFP mutant tended to accumulate in myoblasts but was incorporated into filamentous structures of myotubes. The K49del-b-TMEGFP and E122K-b-TMEGFP mutants induced the formation of rod-like structures in human cells. The N202K-b-TMEGFP mutant failed to integrate into thin filaments and formed accumulations in myotubes. The accumulation of mutant b-TMEGFP in the perinuclear and peripheral areas of the cells was the striking feature in C2C12. We demonstrated that human tissue culture is a suitable system for studying the early stages of altered myofibrilogenesis and morphological changes linked to myopathy-related b-TM mutants. In addition, the histopathological phenotype associated with expression of the various mutant proteins depends on the cell type and varies with the maturation of the muscle cell. Further, the phenotype is a combinatorial effect of the specific amino aci