Complex Arrhythmia Syndrome in a Knock-In Mouse Model Carrier of the N98S Calm1 Mutation.

ABSTRACT:

Background

Calmodulin mutations are associated with arrhythmia syndromes in humans. Exome sequencing previously identified a de novo mutation in CALM1 resulting in a p.N98S substitution in a patient with sinus bradycardia and stress-induced bidirectional ventricular ectopy. The objectives of the present study were to determine if mice carrying the N98S mutation knocked into Calm1 replicate the human arrhythmia phenotype and to examine arrhythmia mechanisms.

Methods

Mouse lines heterozygous for the Calm1^N98S allele (Calm1^N98S/+) were generated using CRISPR/Cas9 technology. Adult mutant mice and their wildtype littermates (Calm1^+/+) underwent electrocardiographic monitoring. Ventricular de- and repolarization was assessed in isola

SUBMITTER: Tsai WC 

PROVIDER: S-EPMC7867118 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature