FVB/N-Tg(Myh6-Tpm1*E54K)67Dfw/MskfJ

Stock number: 035610
Product name: α-TM54
Research areas: Cardiovascular Research, Internal/Organ Research

Description

TM54 transgenic mice express a cardiac-specific Tpm1 (tropomyosin 1, alpha) gene modified to incorporate the E54K mutation associated with dilated cardiomyopathy 1Y. Hemizygous mice exhibit dilated cardiomyopathy with 38% of mice dying by 8 months. This strain may be useful in studies of dilated cardiomyopathy.

Detailed description

Tpm1 (tropomyosin 1, alpha) encodes a striated muscle thin filament protein that binds actin filaments and provides structural stability as well as regulation of filament function. TPM1 is involved in the regulation of muscle contraction through Ca2+-mediated activation through the troponin complex. Mutations in Tpm1 are associated with dilated and hypertrophic cardiomyopathy. TM54 mice express a murine Tpm1 harboring a glutamic acid to lysine substitution at residue 54 (E54K) under the cardiomyocyte-specific Myh6 promoter. The E54K mutation is associated with dilated cardiomyopathy 1Y. Mice hemizygous for the mutation are viable and fertile but begin dying of heart failure between 4-6 months with 38% dying by 8 months. TM54 mice develop peripheral edema, increased heart weight, dilation of both ventricles, peripheral edema, and myocyte hypertrophy.

A companion strain, TM180, carrying the hypertrophic cardiomyopathy E180G mutation in Tpm1 is available as Stock No. 035611.

Development

The α-TM54 transgenic construct contains mutant mouse Tpm1 (tropomyosin 1, alpha) cDNA followed by a polyA tail under the control of the cardiac specific Myh6 (α-myosin heavy chain) promoter. The TM54 mutation replaces a glutamic acid (GAA) at residue 54 with a lysine (AAA) (E54K) in exon 3 of the expression construct. The linearized construct was microinjected into fertilized FVB/N oocytes. Founder 67 carrying 22 copies of the transgene was maintained on FVB/N. Upon arrival, mice were bred to FVB/NJ (Stock No. 001800) for at least 1 generation to establish the colony.

Allele

Symbol: Tg(Myh6-Tpm1*E54K)67Dfw
Name: transgene insertion 67, David F Wieczorek
MGI accession ID: MGI:5906017
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: alpha-TM54
Marker symbol: Tg(Myh6-Tpm1*E54K)67Dfw
Marker name: transgene insertion 67, David F Wieczorek
Marker synonyms: alpha-TM54
Chromosome: UN
Strain of origin: FVB/N
Site of expression: cardiomyocytes
Molecular note: The cardiac specific mouse alpha-MHC promoter drives the expression of a mouse mutant alpha-tropomyosin striated muscle specific cDNA with a single nucleotide change, GAA>AAA, corresponding to an amino acid substitution of a glutamic acid to lysine at codon 54 (Glu54Lys). Five lines were generated; 67, 71, 76, 95, and 30. This line has a copy number of 22 and is one of the moderate-expressing lines.