Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N3pN1 Generation Definitions   Donating Investigator Jeffery D. Molkentin,   Children's Hospital Medical Center

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.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Gata4

006807	B6Ei.129S6(Cg)-Gata4tm1.1Sho/EiJ
006808	D2.129S6(Cg)-Gata4tm1.1Sho/EiJ
008194	STOCK Gata4tm1.1Sad/J
018121	STOCK Gata4tm3.1Wtp Gt(ROSA)26Sortm1(birA)Mejr/J
016572	STOCK Tg(Myh6/tetO-Gata4)1Jmol/J

View Strains carrying other alleles of Gata4     (5 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Atrial Septal Defect 2; ASD2   (GATA4) Atrioventricular Septal Defect 4; AVSD4   (GATA4) Ventricular Septal Defect 1; VSD1   (GATA4)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Gata4^tm1.1Jmol/Gata4^tm1.1Jmol

        involves: 129 * C57BL/6

• cardiovascular system phenotype
• abnormal heart ventricle morphology
  • heart ventricular weight normalized to body weight is slightly but significantly decreased at 8 weeks of age   (MGI Ref ID J:174537)
• altered response of heart to induced stress
  • after 2 weeks of transverse aortic constriction induced pressure overload, left ventricular dilation and reduced fractional shortening are seen suggesting cardiac failure with dilation   (MGI Ref ID J:174537)
  • after 2 weeks of pressure overload cardiomyocytes show signs of eccentric remodeling and enhanced fibrosis   (MGI Ref ID J:174537)
• • decreased response of heart to induced stress
    • the hypertrophic response induced by prolonged (2 week) exposure to phenylephrine is significantly blunted   (MGI Ref ID J:174537)
    • the hypertrophic response to 1 week of pressure overload is significantly blunted   (MGI Ref ID J:174537)
• homeostasis/metabolism phenotype
• altered response of heart to induced stress
  • after 2 weeks of transverse aortic constriction induced pressure overload, left ventricular dilation and reduced fractional shortening are seen suggesting cardiac failure with dilation   (MGI Ref ID J:174537)
  • after 2 weeks of pressure overload cardiomyocytes show signs of eccentric remodeling and enhanced fibrosis   (MGI Ref ID J:174537)
• • decreased response of heart to induced stress
    • the hypertrophic response induced by prolonged (2 week) exposure to phenylephrine is significantly blunted   (MGI Ref ID J:174537)
    • the hypertrophic response to 1 week of pressure overload is significantly blunted   (MGI Ref ID J:174537)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cardiovascular Research
Heart Abnormalities
      cardiomyopathy

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Gata4tm1.1Jmol
Allele Name		targeted mutation 1.1, Jeffery D Molkentin
Allele Type		Targeted (knock-in)
Common Name(s)		Gata4-S105A; S105A;
Mutation Made By		Jeffery Molkentin,   Children's Hospital Medical Center
Strain of Origin		129
Promoter		Gata4, GATA binding protein 4, mouse, laboratory
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. [MGI Ref ID J:174537]

Genotyping

Genotyping Information

Genotyping Protocols

Gata4^tm1.1Jmol, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

van Berlo JH; Elrod JW; Aronow BJ; Pu WT; Molkentin JD. 2011. Serine 105 phosphorylation of transcription factor GATA4 is necessary for stress-induced cardiac hypertrophy in vivo. Proc Natl Acad Sci U S A 108(30):12331-6. [PubMed: 21746915]  [MGI Ref ID J:174537]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	Heterozygotes or homozygotes may be bred.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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