# A kinase-dead natural polymorphism in the canine Tnni3k gene

## TL;DR

A natural mutation in a dog gene linked to heart cell development could affect heart regeneration abilities in multiple species.

## Contribution

Discovery of a kinase-dead polymorphism in the canine Tnni3k gene associated with heart cell diploidy and regeneration.

## Key findings

- A polymorphism in the canine Tnni3k gene is common in West Highland White Terriers.
- The variant eliminates Tnni3k kinase activity, potentially affecting heart cell diploidy and regeneration.
- Natural Tnni3k polymorphisms exist across species, influencing heart regenerative capacity.

## Abstract

Most mammalian cardiomyocytes become polyploid in the neonatal period, concurrent with their loss of proliferative capacity. In mice, natural or engineered mutation of the cardiomyocyte-specific kinase gene
Tnni3k
causes a higher level of diploid CMs and a higher capacity to support proliferation after adult injury. Here, we identified a polymorphism in the canine
Tnni3k
gene that is particularly common in the West Highland White Terrier breed, and show that this variant eliminates Tnni3k kinase activity. Thus, in several species, natural Tnni3k polymorphisms exist that are predicted to contribute to variation in diploid CM level and heart regenerative ability.