Phenotypes of myopathy-related beta-tropomyosin mutants in human and mouse tissue cultures.
PLoS One
; 8(9): e72396, 2013.
Article
em En
| MEDLINE
| ID: mdl-24039757
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 ß-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-ß-TM(EGFP) mutant showed perinuclear aggregates. The G53ins-ß-TM(EGFP) mutant tended to accumulate in myoblasts but was incorporated into filamentous structures of myotubes. The K49del-ß-TM(EGFP) and E122K-ß-TM(EGFP) mutants induced the formation of rod-like structures in human cells. The N202K-ß-TM(EGFP) mutant failed to integrate into thin filaments and formed accumulations in myotubes. The accumulation of mutant ß-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 ß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tropomiosina
/
Fibras Musculares Esqueléticas
/
Doenças Musculares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Suécia