Two zebrafish cacna1s loss-of-function variants provide models of mild and severe CACNA1S-related myopathy.

ABSTRACT: CACNA1S-related myopathy, due to pathogenic variants in the CACNA1S gene, is a recently described congenital muscle disease. Disease associated variants result in loss of gene expression and/or reduction of Cav1.1 protein stability. There is an incomplete understanding of the underlying disease pathomechanisms and no effective therapies are currently available. A barrier to the study of this myopathy is the lack of a suitable animal model that phenocopies key aspects of the disease. To address this barrier, we generated knockouts of the two zebrafish CACNA1S paralogs, cacna1sa and cacna1sb. Double knockout fish exhibit severe weakness and early death, and are characterized by the absence of Cav1.1 α1 subunit expression, abnormal triad structure, and impaired excitation-contraction coupling

SUBMITTER: Endo Y 

PROVIDER: S-EPMC10800018 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature