This report describes fly models relevant to cardiomyopathies that are TPM1-related. The human gene implicated in these diseases (TPM1) encodes the actin binding protein tropomyosin 1; TPM1 protein plays a role in striated muscle contraction. TPM1 is implicated in several forms of heart disease (see MIM:191010), including CMD1Y (FBhh0000164) and CMH3 (FBhh0000417); cardiomyopathy-associated variants act as autosomal dominants. Involvement of TPM1 with both dilated cardiomyopathy and hypertrophic cardiomyopathy is strongly supported by a large-scale WES analysis (Walsh, et al., 2016; pubmed:27532257).
The human Hsap\TPM1 gene has been introduced into flies, but has not been characterized; a stock is available.
There are multiple tropomyosin genes in both species (4 human to 2 Drosophila). The two orthologous fly genes are Dmel\Tm1 and Dmel\Tm2. RNAi targeting constructs, alleles caused by insertional mutagenesis, and regulated expression constructs have been generated for both genes; classical loss-of-function mutations have been generated for Tm2. Cardiomyopathy has been investigated using Tm2. Animals homozygous for amorphic mutations of Tm2 typically die during late embryo stage; less severe mutants exhibit defects in embryonic/larval muscle, in the embryonic/larval heart, and in adult flight behavior.
[updated Mar. 2024 by FlyBase; FBrf0222196]
Tropomyosins are dimers of coiled-coil proteins that provide stability to actin filaments and regulate access of other actin-binding proteins. TPM1 is one type of alpha helical chain that forms the predominant tropomyosin of striated muscle; it functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. [from Gene Cards, TPM1 gene, TPM3 gene; 2016.10.29]
Tropomyosins are a family of actin-binding proteins encoded by 4 distinct genes. Each gene generates multiple striated muscle, smooth muscle, and cytoskeletal variants by alternative splicing, alternative promoter usage, and differential 3-prime end processing. Of the 4 human tropomyosin genes, TPM1 is the most versatile and encodes at least 10 tissue-specific variants via alternative splicing and/or the use of 2 promoters. The TPM1 variants encode proteins of either 248 or 284 amino acids (summary by Denz et al., 2004, pubmed:15249230). [From MIM:191010, 2016.02.02]
Many to many: 4 human to 2 Drosophila; the additional human genes are TPM2, TPM3, and TPM4.
Ortholog of human TPM1, TPM2, TPM3, and TPM4 (2 Drosophila to 4 human). Dmel\Tm2 shares 46-47% identity and 67-70% similarity with the human genes.
