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General Information
Name
cardiomyopathy, TNNT2-related
FlyBase ID
FBhh0000419
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes fly models relevant to cardiomyopathies that are TNNT2-related. The human gene implicated in these diseases (TNNT2) cardiac-type troponin T, a component of sarcomere thin filaments. TNNT2 is implicated in several forms of heart disease (see OMIM:191045), including CMD1D (FBhh0000163), CMH2 (FBhh0000413), and familial restrictive cardiomyopathy 3 (OMIM:612422); cardiomyopathy-associated variants act as autosomal dominants. Involvement of TNNT2 with both dilated cardiomyopathy and hypertrophic cardiomyopathy is supported by a large-scale WES analysis (Walsh, et al., 2016; pubmed:27532257).

There is one fly ortholog of TNNT2, up; Dmel\up is also orthologous to human genes TNNT1 and TNNT3, which are described as skeletal-type troponins. RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical missense alleles have been generated for the up gene. Animals homozygous for mutant alleles survive to adulthood, but are flightless and exhibit and abnormal wing posture; after eclosion, indirect flight muscles exhibit hypercontraction and progressive degeneration. Genetic and physical interactions of Dmel\up have been described; see below and the up gene report.

A UAS construct of a tagged wild-type human Hsap\TNNT2 gene has been introduced into flies, but has not been used to characterize this disease model.

[updated Oct. 2016 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cardiomyopathy, TNNT2-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

The troponin complex is located on the thin filament of striated muscle and is composed of 3 component polypeptides: troponin T (TNNT1, OMIM:191041; and TNNT2), troponin I (TNNI1, OMIM:191042; TNNI2, OMIM:191043; and TNNI3, OMIM:191044), and troponin C (TNNC1, OMIM:191040; and TNNC2 OMIM:191039). Three troponin T genes have been described on the basis of molecular cloning in humans and other vertebrates. These are expressed in a tissue-specific manner and encode the troponin T isoforms expressed in cardiac muscle, slow skeletal muscle (TNNT1), and fast skeletal muscle (TNNT3; OMIM:600692). Each of these genes is subject to alternative splicing, resulting in the production of multiple tissue-specific isoforms. [From OMIM:191045, 2016.02.02]

External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 3 human to 1 Drosophila; additional human orthologs are TNNT1 and TNNT3. TNNT2 is described as cardiac-type T troponin; TNNT1 and TNNT3 are described as skeletal-type T troponins.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    upheld (up) encodes the striated muscle protein Troponin T. Troponins T, C and I form a regulatory complex with Tropomyosin that is found at regular intervals along the thin (F-actin) filaments of the muscle sarcomere. [Date last reviewed: 2019-03-21]
    Gene Groups / Pathways
      Comments on ortholog(s)

      Ortholog of human TNNT2, TNNT1, and TNNT3 (1 Drosophila to 3 human). Dmel\up shares 32-37% identity and 47-54% similarity with the human genes.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (41 groups)
      protein-protein
      Interacting group
      Assay
      References
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      anti tag coimmunoprecipitation, peptide massfingerprinting
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      anti tag coimmunoprecipitation, Identification by mass spectrometry
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      RNA-RNA
      Interacting group
      Assay
      References
      western blot, quantitative reverse transcription pcr
      Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
      Models Based on Experimental Evidence ( 2 )
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
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      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      p-N,N-di-(2-chloroethyl)amino-DL-phenylalanine
      ethyl methanesulfonate
      References (13)