Genetic compensation triggered by actin mutation prevents the muscle damage caused by loss of actin protein.
PLoS Genet
; 14(2): e1007212, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29420541
ABSTRACT
The lack of a mutant phenotype in homozygous mutant individuals' due to compensatory gene expression triggered upstream of protein function has been identified as genetic compensation. Whilst this intriguing process has been recognized in zebrafish, the presence of homozygous loss of function mutations in healthy human individuals suggests that compensation may not be restricted to this model. Loss of skeletal α-actin results in nemaline myopathy and we have previously shown that the pathological symptoms of the disease and reduction in muscle performance are recapitulated in a zebrafish antisense morpholino knockdown model. Here we reveal that a genetic actc1b mutant exhibits mild muscle defects and is unaffected by injection of the actc1b targeting morpholino. We further show that the milder phenotype results from a compensatory transcriptional upregulation of an actin paralogue providing a novel approach to be explored for the treatment of actin myopathy. Our findings provide further evidence that genetic compensation may influence the penetrance of disease-causing mutations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mecanismo Genético de Compensação de Dose
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Actinas
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Miopatias da Nemalina
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Músculo Esquelético
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
PLoS Genet
Assunto da revista:
GENETICA
Ano de publicação:
2018
Tipo de documento:
Article