Tnni3k, short for troponin I-interacting kinase, is a kinase mainly expressed in the heart. It has been implicated in multiple cardiac-related physiological processes, and human genetic variants in Tnni3k are associated with supraventricular arrhythmias, conduction disease, and cardiomyopathy [1,2,5]. Its role in cardiac-related pathways and overall biological importance lies in its potential influence on cardiac function, cell cycle regulation in cardiomyocytes, and heart regenerative capacity [1,3,4]. Genetic models, especially mouse models, have been crucial for studying Tnni3k.

In mouse studies, Tnni3k has been shown to influence cardiomyocyte S-phase activity and proliferation, indicating its role in the cell cycle of cardiomyocytes [3]. Tnni3k alleles also affect the frequency of ventricular mononuclear diploid cardiomyocytes, a proliferative and regenerative subpopulation of the postnatal heart [4]. Some common human TNNI3K kinase domain variants compromise kinase activity, suggesting implications for human heart regenerative capacity and disease [4].

In conclusion, Tnni3k plays essential roles in cardiac-related functions, especially in cardiomyocyte proliferation and the regulation of specific cardiomyocyte subpopulations. Mouse models, such as KO/CKO mouse models, have been instrumental in revealing these functions, contributing to our understanding of its role in cardiac diseases like cardiomyopathy, arrhythmias, and potentially heart failure [1,2,3,4,5].

References:

1. Pham, Caroline, Muñoz-Martín, Noelia, Lodder, Elisabeth M. 2021. The Diverse Roles of TNNI3K in Cardiac Disease and Potential for Treatment. In International journal of molecular sciences, 22, . doi:10.3390/ijms22126422. https://pubmed.ncbi.nlm.nih.gov/34203974/

2. Milano, Annalisa, Lodder, Elisabeth M, Bezzina, Connie R. 2015. TNNI3K in cardiovascular disease and prospects for therapy. In Journal of molecular and cellular cardiology, 82, 167-73. doi:10.1016/j.yjmcc.2015.03.008. https://pubmed.ncbi.nlm.nih.gov/25787061/

3. Purdy, Alexandra L, Swift, Samantha K, Sucov, Henry M, Patterson, Michaela. 2023. Tnni3k influences cardiomyocyte S-phase activity and proliferation. In Journal of molecular and cellular cardiology, 183, 22-26. doi:10.1016/j.yjmcc.2023.08.004. https://pubmed.ncbi.nlm.nih.gov/37597489/

4. Gan, Peiheng, Patterson, Michaela, Velasquez, Alexa, Park, Thomas J, Sucov, Henry M. 2019. Tnni3k alleles influence ventricular mononuclear diploid cardiomyocyte frequency. In PLoS genetics, 15, e1008354. doi:10.1371/journal.pgen.1008354. https://pubmed.ncbi.nlm.nih.gov/31589606/

5. Pham, Caroline, Andrzejczyk, Karolina, Jurgens, Sean J, Bezzina, Connie R, Lodder, Elisabeth M. 2023. Genetic Burden of TNNI3K in Diagnostic Testing of Patients With Dilated Cardiomyopathy and Supraventricular Arrhythmias. In Circulation. Genomic and precision medicine, 16, 328-336. doi:10.1161/CIRCGEN.122.003975. https://pubmed.ncbi.nlm.nih.gov/37199186/