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.
Jeffery D. Molkentin, Cincinnati Children's Hospital
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.
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 Name||targeted mutation 1.1, Jeffery D Molkentin|
|Allele Synonym(s)||Gata4-S105A; S105A|
|Gene Symbol and Name||Gata4, GATA binding protein 4|
|Promoter||Gata4, GATA binding protein 4, mouse, laboratory|
|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.|
|Mutations Made By|| |
Jeffery Molkentin, Cincinnati Children's Hospital
Heterozygotes or homozygotes may be bred.
When using the STOCK Gata4tm1.1Jmol/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017544 in your Materials and Methods section.