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. 2024 May 16:2024:10.17912/micropub.biology.001164.
doi: 10.17912/micropub.biology.001164. eCollection 2024.

A kinase-dead natural polymorphism in the canine Tnni3k gene

Baylee C Westbury #  1 , Hirofumi Watanabe #  1   2 , Henry M Sucov  1
Affiliations

A kinase-dead natural polymorphism in the canine Tnni3k gene

Baylee C Westbury et al. MicroPubl Biol. .

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.

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Conflict of interest statement

The authors declare that there are no conflicts of interest present.

Figures

Figure 1. In vitro kinase assay
Figure 1. In vitro kinase assay
Tnni3k wild-type (WT) and M573I expression plasmids have an N-terminal FLAG epitope that was used for immunoprecipitation. Tnni3k was isolated from transfected HEK293 cell lysates and incubated without (-) or with (+) ATP. Without ATP shows the basal level of Tnni3k phosphorylation as isolated from cells (low because of cellular phosphatases); with ATP shows the autophosphorylation activity of the purified protein. After incubation, Western blotting was performed by probing for phospho-Tyr (pTyr). A parallel blot for FLAG detection shows similar loading.
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