Format

Send to

Choose Destination
PLoS Genet. 2018 Feb 8;14(2):e1007212. doi: 10.1371/journal.pgen.1007212. eCollection 2018 Feb.

Genetic compensation triggered by actin mutation prevents the muscle damage caused by loss of actin protein.

Author information

1
School of Biological Sciences, Monash University, Melbourne, Victoria Australia.

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.

PMID:
29420541
PMCID:
PMC5821405
DOI:
10.1371/journal.pgen.1007212
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center