The prevalent I686T human variant and loss-of-function mutations in the cardiomyocyte-specific kinase gene TNNI3K cause adverse contractility and concentric remodeling in mice.

ABSTRACT: TNNI3K expression worsens disease progression in several mouse heart pathology models. TNNI3K expression also reduces the number of diploid cardiomyocytes, which may be detrimental to adult heart regeneration. However, the gene is evolutionarily conserved, suggesting a beneficial function that has remained obscure. Here, we show that C57BL/6J-inbred Tnni3k mutant mice develop concentric remodeling, characterized by ventricular wall thickening and substantial reduction of cardiomyocyte aspect ratio. This pathology occurs in mice carrying a Tnni3k null allele, a K489R point mutation rendering the protein kinase-dead, or an allele corresponding to human I686T, the most common human non-synonymous TNNI3K variant, which is hypomorphic for kinase activity. Mutant mice develop these conditions in

SUBMITTER: Gan P 

PROVIDER: S-EPMC7788294 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature