Tnni3-flox Mouse

Tnni3, which encodes for the cardiac isoform of troponin I, is a pivotal component of the sarcomeric structure of the myocardium. Troponin I is the inhibitory subunit of the troponin complex in the sarcomeric thin filament of striated muscle, playing a central role in the calcium regulation of contraction and relaxation [2].

Homozygous Tnni3 null mutations have been found to cause a severe form of neonatal dilated cardiomyopathy. For example, two unrelated patients with early onset dilated cardiomyopathy due to homozygosity for certain Tnni3 variants were reported. One had the p.Arg98* Tnni3 variant, previously seen only in heterozygous patients and healthy carriers, and the other had the recurrent p.Arg69Alafs*8 variant [1]. Also, a consanguineous family with three deceased offspring at 1-year-old due to lethal infantile dilated cardiomyopathy was found to have a homozygous frameshift variant in the Tnni3 gene (c.204delG; p.(Arg69AlafsTer8)) [4]. Pathogenic variants in Tnni3, along with TNNT2, are associated with more severe clinical outcomes in childhood cardiomyopathy [3].

In conclusion, Tnni3 is crucial for the normal function of the myocardium, specifically in the calcium-regulated contraction and relaxation process. Studies on Tnni3-related mutations in humans have revealed its significant role in severe early-onset dilated cardiomyopathy and childhood cardiomyopathy, highlighting the importance of understanding Tnni3 function for the diagnosis and prognosis of these cardiac diseases.