title: Phenotypes of myopathy-related beta-tropomyosin mutants in human and mouse tissue cultures.
abstract: 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 β-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-β-TM(EGFP) mutant showed perinuclear aggregates. The G53ins-β-TM(EGFP) mutant tended to accumulate in myoblasts but was incorporated into filamentous structures of myotubes. The K49del-β-TM(EGFP) and E122K-β-TM(EGFP) mutants induced the formation of rod-like structures in human cells. The N202K-β-TM(EGFP) mutant failed to integrate into thin filaments and formed accumulations in myotubes. The accumulation of mutant β-TM(EGFP) 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 β-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 acid change and the temporal expression of the mutant protein.
authors.affiliation: Department of Pathology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Saba
authors.initials: S
authors.lastname: Abdul-Hussein
authors.forename: Karin
authors.initials: K
authors.lastname: Rahl
authors.forename: Ali-Reza
authors.initials: AR
authors.lastname: Moslemi
authors.forename: Homa
authors.initials: H
authors.lastname: Tajsharghi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D015870:Gene Expression; D056726:Genetic Association Studies; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D032446:Myoblasts / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012518:Sarcomeres / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D046509:Tissue Culture Techniques; D014335:Tropomyosin / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D014335:Tropomyosin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
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