MICE THAT OVEREXPRESS A FRAMESHIFT MUTATION IN HUMAN NATRIURETIC PEPTIDE PRECURSOR A GENE EXHIBIT INCREASED ATRIAL FIBRILLATION BURDEN BUT NO ATRIAL STRUCTURAL REMODELING.

Abstract

A frameshift mutation in natriuretic peptide precursor A gene (NPPA) encoding a mutant atrial natriuretic peptide (ANP) has been linked with familial atrial fibrillation (AF). Mutant ANP shortened monophasic action potential duration and effective refractory period in retrogradely perfused rat hearts suggesting a potential mechanism for AF. We engineered 2 transgenic mouse lines that overexpress either mutant human NPPA (h-M) or human wild-type NPPA (h-WT) to test the hypothesis that h-M mice are more prone to develop AF.