Strain Name:

STOCK Gata4tm1.1Sad/J

Stock Number:

008194

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Availability:

Cryopreserved - Ready for recovery

These GATA binding protein 4 conditional mice may be useful in generating conditional mutations for studying GATA4 function during organogenesis (such as cardiogenesis) or in adult mice.

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.
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Specieslaboratory mouse
 
Donating Investigator Stephen Duncan,   Medical College of Wisconsin

Description
Mice homozygous for this Gata4loxP conditional allele are viable and fertile, with loxP sites flanking exons 3-5 of the targeted gene. When bred to mice that express Cre recombinase, the resulting offspring will have this region (coding for both zinc finger DNA-binding domains and the nuclear localization signal essential for GATA4 function) deleted in the cre-expressing tissue(s). These GATA binding protein 4 conditional mice may be useful in generating conditional mutations for studying GATA4 function during organogenesis (such as cardiogenesis) or in adult mice.

For example, when crossed to a strain expressing Cre recombinase in cardiac myocytes (see Stock No. 009074), this mutant mouse strain may be useful in studies of cardiac hypertrophy, stress-compensation and myocyte viability.

When bred to a strain expressing Cre recombinase in heart muscle (see Stock No. 010581 for example), this mutant mouse strain may be useful in studies of cardiac hypertrophy.

Development
A targeting vector was designed to place a loxP-flanked thymidine kinase/neomycin phosphotransferase expression (tk/neo) cassette upstream of exon 3, and a third loxP site just downstream of exon 5 of the targeted gene. The targeting construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre expressing plasmid to remove the selection cassette (generating the Gata4loxP allele; with one loxP site upstream of exon 3 and one loxP site downstream of exon 5). These ES cells were combined with CD1 morula to generate chimeric animals, which were then bred with CD1 mice. These Gata4loxP mice were maintained on a mixed genetic background prior to arrival at The Jackson Laboratory. Upon arrival, mice may have been bred to 129S1/SvImJ for at least one generation to establish the colony.

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Gata4     (7 strains)

Additional Web Information

Introduction to Cre-lox technology

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)
Testicular Anomalies with or without Congenital Heart Disease; TACHD   (GATA4)
Ventricular Septal Defect 1; VSD1   (GATA4)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
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Gata4tm1.1Sad/Gata4tm1.1Sad Tg(Myh6-Map2k1*)1Jmol/0

        involves: 129S1/Sv * 129X1/SvJ * FVB
  • cardiovascular system phenotype
  • cardiac hypertrophy
    • about a 30% increase in ventricular weight compared to mutant mice not carrying the transgene   (MGI Ref ID J:174537)

Gata4tm1.1Sad/Gata4tm1.1Sad Tg(Myh6-cre)1Jmk/0

        involves: 129S1/Sv * 129X1/SvJ * CD-1   (conditional)
  • cardiovascular system phenotype
  • abnormal myocardial fiber morphology
    • 30% of cells having Gata4 expression are larger than Gata4-deficient cells in the heart   (MGI Ref ID J:121367)
  • decreased cardiac muscle contractility
    • significant reduction of fractional shortening is observed at 24 weeks   (MGI Ref ID J:121367)
  • dilated heart
    • heart displays dilation, but this is less prominent than if deletion is produced by Tg(Myh7-cre)1Jmk   (MGI Ref ID J:121367)
  • muscle phenotype
  • abnormal myocardial fiber morphology
    • 30% of cells having Gata4 expression are larger than Gata4-deficient cells in the heart   (MGI Ref ID J:121367)
  • decreased cardiac muscle contractility
    • significant reduction of fractional shortening is observed at 24 weeks   (MGI Ref ID J:121367)
  • respiratory system phenotype
  • pulmonary edema
    • following transverse aortic constriction (TAC), severe pulmonary edema is observed   (MGI Ref ID J:121367)
  • homeostasis/metabolism phenotype
  • pulmonary edema
    • following transverse aortic constriction (TAC), severe pulmonary edema is observed   (MGI Ref ID J:121367)
View Research Applications

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

Research Tools
Cardiovascular Research
      Cre-lox System
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Gata4tm1.1Sad
Allele Name targeted mutation 1.1, Stephen A Duncan
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) Gata4loxP;
Mutation Made By Stephen Duncan,   Medical College of Wisconsin
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Gata4, GATA binding protein 4
Chromosome 14
Gene Common Name(s) ASD2; Gata-4; TACHD; VSD1;
Molecular Note A targeting vector was designed to place a loxP-flanked thymidine kinase/neomycin phosphotransferase expression (tk/neo) cassette upstream of exon 3, and a third loxP site just downstream of exon 5 of the targeted gene. Correctly targeted ES cells were transiently transfected with a cre expressing plasmid to remove the selection cassette (generating the Gata4-loxP allele; with one loxP site upstream of exon 3 and one loxP site downstream of exon 5). (details provided by SA Duncan, personal communication.) [MGI Ref ID J:92434]

Genotyping

Genotyping Information

Genotyping Protocols

Gata4tm1.1Sad, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Watt AJ; Battle MA; Li J; Duncan SA. 2004. GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. Proc Natl Acad Sci U S A 101(34):12573-8. [PubMed: 15310850]  [MGI Ref ID J:92434]

Additional References

Gata4tm1.1Sad related

Battle MA; Bondow BJ; Iverson MA; Adams SJ; Jandacek RJ; Tso P; Duncan SA. 2008. GATA4 is essential for jejunal function in mice. Gastroenterology 135(5):1676-1686.e1. [PubMed: 18812176]  [MGI Ref ID J:145635]

Heineke J; Auger-Messier M; Xu J; Oka T; Sargent MA; York A; Klevitsky R; Vaikunth S; Duncan SA; Aronow BJ; Robbins J; Cromblehol TM; Molkentin JD. 2007. Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart. J Clin Invest 117(11):3198-210. [PubMed: 17975667]  [MGI Ref ID J:127378]

Hu YC; Okumura LM; Page DC. 2013. Gata4 is required for formation of the genital ridge in mice. PLoS Genet 9(7):e1003629. [PubMed: 23874227]  [MGI Ref ID J:199295]

Kolander KD; Holtz ML; Cossette SM; Duncan SA; Misra RP. 2014. Epicardial GATA factors regulate early coronary vascular plexus formation. Dev Biol 386(1):204-15. [PubMed: 24380800]  [MGI Ref ID J:206877]

Krachulec J; Vetter M; Schrade A; Lobs AK; Bielinska M; Cochran R; Kyronlahti A; Pihlajoki M; Parviainen H; Jay PY; Heikinheimo M; Wilson DB. 2012. GATA4 is a critical regulator of gonadectomy-induced adrenocortical tumorigenesis in mice. Endocrinology 153(6):2599-611. [PubMed: 22461617]  [MGI Ref ID J:186730]

Kyronlahti A; Euler R; Bielinska M; Schoeller EL; Moley KH; Toppari J; Heikinheimo M; Wilson DB. 2011. GATA4 regulates Sertoli cell function and fertility in adult male mice. Mol Cell Endocrinol 333(1):85-95. [PubMed: 21172404]  [MGI Ref ID J:169018]

Kyronlahti A; Vetter M; Euler R; Bielinska M; Jay PY; Anttonen M; Heikinheimo M; Wilson DB. 2011. GATA4 deficiency impairs ovarian function in adult mice. Biol Reprod 84(5):1033-44. [PubMed: 21248289]  [MGI Ref ID J:173711]

Oka T; Maillet M; Watt AJ; Schwartz RJ; Aronow BJ; Duncan SA; Molkentin JD. 2006. Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability. Circ Res 98(6):837-45. [PubMed: 16514068]  [MGI Ref ID J:121367]

Ounzain S; Kobayashi S; Peterson RE; He A; Motterle A; Samani NJ; Menick DR; Pu WT; Liang Q; Chong NW. 2012. Cardiac expression of ms1/STARS, a novel gene involved in cardiac development and disease, is regulated by GATA4. Mol Cell Biol 32(10):1830-43. [PubMed: 22431517]  [MGI Ref ID J:185738]

Patankar JV; Chandak PG; Obrowsky S; Pfeifer T; Diwoky C; Uellen A; Sattler W; Stollberger R; Hoefler G; Heinemann A; Battle M; Duncan S; Kratky D; Levak-Frank S. 2011. Loss of intestinal GATA4 prevents diet-induced obesity and promotes insulin sensitivity in mice. Am J Physiol Endocrinol Metab 300(3):E478-88. [PubMed: 21177287]  [MGI Ref ID J:172316]

Rawnsley DR; Xiao J; Lee JS; Liu X; Mericko-Ishizuka P; Kumar V; He J; Basu A; Lu M; Lynn FC; Pack M; Gasa R; Kahn ML. 2013. The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development. J Biol Chem 288(34):24429-40. [PubMed: 23836893]  [MGI Ref ID J:203454]

Warren SA; Terada R; Briggs LE; Cole-Jeffrey CT; Chien WM; Seki T; Weinberg EO; Yang TP; Chin MT; Bungert J; Kasahara H. 2011. Differential role of Nkx2-5 in activation of the atrial natriuretic factor gene in the developing versus failing heart. Mol Cell Biol 31(22):4633-45. [PubMed: 21930795]  [MGI Ref ID J:178775]

Xuan S; Borok MJ; Decker KJ; Battle MA; Duncan SA; Hale MA; Macdonald RJ; Sussel L. 2012. Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis. J Clin Invest 122(10):3516-28. [PubMed: 23006325]  [MGI Ref ID J:192748]

Zheng R; Rebolledo-Jaramillo B; Zong Y; Wang L; Russo P; Hancock W; Stanger BZ; Hardison RC; Blobel GA. 2013. Function of GATA factors in the adult mouse liver. PLoS One 8(12):e83723. [PubMed: 24367609]  [MGI Ref ID J:211132]

van Berlo JH; Aronow BJ; Molkentin JD. 2013. Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response. PLoS One 8(12):e84591. [PubMed: 24391969]  [MGI Ref ID J:209830]

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]

van Berlo JH; Elrod JW; van den Hoogenhof MM; York AJ; Aronow BJ; Duncan SA; Molkentin JD. 2010. The transcription factor GATA-6 regulates pathological cardiac hypertrophy. Circ Res 107(8):1032-40. [PubMed: 20705924]  [MGI Ref ID J:171966]

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 & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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