STOCK Gata4^tm1.1Jmol/J

Stock number: 017544
Research areas: Cardiovascular Research

Description

Serine 105 of the mouse Gata4 (GATA binding protein 4) gene was mutated to an alanine in this targeted mutation strain. Homozygotes show a compromised stress response of the myocardium and are also more susceptible to heart failure and cardiac dilation.

Detailed description

Gata4 (GATA binding protein 4) is expressed in mesoderm-derived tissues such as the heart, liver, gut and gonads. It is a critical transcription factor in the heart that is known to induce/regulate the hypertrophic program, in part, by receiving signals from MAPKs.

In this targeted mutation strain, serine 105 of the mouse Gata4 gene was changed to an alanine to disrupt a known MAPK phosphorylation site. Homozygotes are viable, fertile, and born at predicted Mendelian frequencies. Mice show a compromised stress response of the myocardium. Cardiac hypertrophy in response to phenylephrine agonist infusion and pressure overload are largely blunted. Homozygotes are also more susceptible to heart failure and cardiac dilation after 2 weeks of pressure overload.

Development

Serine 105 of the targeted gene (located in exon 2) was mutated to an alanine (S105A) and an FRT-flanked neomycin selection cassette was introduced to intron 2. A 129-derived embryonic stem (ES) cell line was used to create the mutation. A cross with a germline/testes-specific FLP strain of unknown genetic background excised the neomycin cassette. This strain was backcrossed to C57BL/6 for 3 generations by the donating lab.

Allele

Symbol: Gata4^tm1.1Jmol
Name: targeted mutation 1.1, Jeffery D Molkentin
MGI accession ID: MGI:5141274
Generation method: Targeted
Marker symbol: Gata4
Marker name: GATA binding protein 4
Chromosome: 14
Strain of origin: 129
Molecular note: Point mutations were introduced to change serine 105 into alanine and an FRT flanked neo cassette was inserted via homologous recombination. Flp mediated recombination removed the neo cassette. Western blot analysis confirmed the absence of S105 phosphorylated protein and presence of non-phosphorylated protein.