In vivo Dominant-Negative Effect of an SCN5A Brugada Syndrome Variant.

ABSTRACT: Loss-of-function mutations in the cardiac Na⁺ channel α-subunit Na_v1.5, encoded by SCN5A, cause Brugada syndrome (BrS), a hereditary disease characterized by sudden cardiac death due to ventricular fibrillation. We previously evidenced in vitro the dominant-negative effect of the BrS Na_v1.5-R104W variant, inducing retention of wild-type (WT) channels and leading to a drastic reduction of the resulting Na⁺ current (I _Na ). To explore this dominant-negative effect in vivo, we created a murine model using adeno-associated viruses (AAVs).

Methods

Due to the large size of SCN5A, a dual AAV vector strategy was used combining viral DNA recombination and trans-splicing. Mice were injected

SUBMITTER: Doisne N 

PROVIDER: S-EPMC8195286 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature