Tnnt1, encoding slow skeletal muscle troponin T, is one of three homologous genes in vertebrates related to troponin T (TnT) isoforms, with TNNT2 for cardiac muscle TnT and TNNT3 for fast skeletal muscle TnT. TnT is crucial in the calcium regulation of actin thin filament function and striated muscle contraction. Alternative splicing and post-translational modifications further diversify TnT's structure and function during development and muscle adaptation [2].

Compound heterozygous mutations in TNNT1 were found in a Korean family, causing intermediate-phenotype TNNT1 myopathy. Muscle biopsy showed nemaline rods, and exon 11 skipping was confirmed in the patient's muscle cDNA. A zebrafish loss-of-function model verified the missense variant's impact on muscle integrity and locomotor activity [1]. In French Canadians, a novel missense homozygous variant in TNNT1 led to a form of recessive congenital core-rod myopathy. A zebrafish loss-of-function model using morpholinos was created, and wild-type TNNT1 mRNA rescued the zebrafish morphants while mutant transcripts failed, providing functional evidence for the mutation's pathogenicity [3].

In conclusion, TnT1 is essential for the proper contraction of slow skeletal muscles. Studies using zebrafish loss-of-function models have been valuable in revealing the role of TNNT1 mutations in causing nemaline myopathies and other related muscle disorders, providing insights into potential therapeutic strategies for these diseases [1,3].

References:

1. Lee, Seungbok, Eum, Juneyong, Park, Soojin, Kee, Yun, Chae, Jong Hee. 2021. TNNT1 myopathy with novel compound heterozygous mutations. In Neuromuscular disorders : NMD, 32, 176-184. doi:10.1016/j.nmd.2021.12.003. https://pubmed.ncbi.nlm.nih.gov/35165004/

2. Wei, Bin, Jin, J-P. 2016. TNNT1, TNNT2, and TNNT3: Isoform genes, regulation, and structure-function relationships. In Gene, 582, 1-13. doi:10.1016/j.gene.2016.01.006. https://pubmed.ncbi.nlm.nih.gov/26774798/

3. Pellerin, David, Aykanat, Asli, Ellezam, Benjamin, Brais, Bernard, Chrestian, Nicolas. 2020. Novel Recessive TNNT1 Congenital Core-Rod Myopathy in French Canadians. In Annals of neurology, 87, 568-583. doi:10.1002/ana.25685. https://pubmed.ncbi.nlm.nih.gov/31970803/