Strain Name:

B6;129-Dusp6tm1Jmol/J

Stock Number:

009069

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Availability:

Cryopreserved - Ready for recovery

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Homozygous Dusp6 (dual specificity phosphatase 6) knock-out mutant mice have enlarged hearts; cardiac hypercellularity due to greater rates of myocyte proliferation during embryonic development and in the early postnatal period. Embryonic fibroblasts derived from these mice show reduced apoptosis. This strain may be useful in studies of heart function and disease.

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

Former Names B6;129X1-Dusp6tm1Jmol/J    (Changed: 16-APR-12 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation?pN1
Generation Definitions
 
Donating Investigator Jeffery D. Molkentin,   Cincinnati Children's Hospital

Description
Homozygous targeted mutant mice have larger hearts than wild-type mice at every age examined. They show greater rates of myocyte proliferation during embryonic development and in the early postnatal period, resulting in cardiac hypercellularity. This lends protection against decompensation and hypertrophic cardiomyopathy following long term pressure overload and myocardial infarction injury in adult mice. Embryonic fibroblasts derived from these mice also show reduced apoptosis rates as compared to wildtype. Homozygotes are viable, fertile and otherwise overtly normal. This strain may be useful in studies of heart function and disease.

Development
All three exons (exons 1-3) of the gene were replaced with a neomycin resistance gene. A 129-derived embryonic stem (ES) cell line was used to create the mutation. Chimeras were crossed with C57BL/6 and the line was maintained on a mixed C57BL/6 and 129 genetic background by the donating laboratory. At The Jackson Laboratory, the live colony was bred at least one generation to B6129SF2/J mice (Stock No. 101045).

Control Information

  Control
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Dusp6
010578   FVB-Tg(tetO-Dusp6)1Jmol/J
View Strains carrying other alleles of Dusp6     (1 strain)

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.
Hypogonadotropic Hypogonadism 19 with or without Anosmia; HH19   (DUSP6)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Dusp6tm1Jmol/Dusp6tm1Jmol

        involves: 129 * C57BL/6
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype
    • despite the increase in heart size, cardiac function at 1 year of age is similar to controls   (MGI Ref ID J:142966)
    • abnormal heart development
      • at E13.5 a 30% increase in BrdU incorporation is seen in hearts   (MGI Ref ID J:142966)
    • decreased myocardial infarction size
      • following permanent ligation of the left coronary artery the degree of infarct expansion is reduced compared to controls   (MGI Ref ID J:142966)
    • decreased response of heart to induced stress
      • myocyte hypertrophy in response to transverse aortic constriction is reduced compared to controls   (MGI Ref ID J:142966)
      • results from long term transverse aortic constriction suggest homozygotes are partially protected from long term pressure overload induced dysfunction   (MGI Ref ID J:142966)
      • reduced decompensation at 4 weeks after permanent ligation of the left coronary artery   (MGI Ref ID J:142966)
    • heart hyperplasia
      • analysis suggests increased heart size is due to increased cellularity not an increase in cell size   (MGI Ref ID J:142966)
    • increased heart weight
      • increased heart weight relative to body weight compared to controls   (MGI Ref ID J:142966)
  • cellular phenotype
  • decreased sensitivity to induced cell death
    • reduced susceptibility to staurosporine induced apoptosis   (MGI Ref ID J:142966)
  • hematopoietic system phenotype
  • increased spleen weight
    • increased spleen weight relative to body weight compared to controls   (MGI Ref ID J:142966)
  • homeostasis/metabolism phenotype
  • decreased myocardial infarction size
    • following permanent ligation of the left coronary artery the degree of infarct expansion is reduced compared to controls   (MGI Ref ID J:142966)
  • decreased response of heart to induced stress
    • myocyte hypertrophy in response to transverse aortic constriction is reduced compared to controls   (MGI Ref ID J:142966)
    • results from long term transverse aortic constriction suggest homozygotes are partially protected from long term pressure overload induced dysfunction   (MGI Ref ID J:142966)
    • reduced decompensation at 4 weeks after permanent ligation of the left coronary artery   (MGI Ref ID J:142966)
  • immune system phenotype
  • increased spleen weight
    • increased spleen weight relative to body weight compared to controls   (MGI Ref ID J:142966)
  • muscle phenotype
  • *normal* muscle phenotype
    • at 2 months, untreated mice exhibit normal skeletal muscle tissue morphology   (MGI Ref ID J:190460)
    • abnormal muscle physiology
      • at 2 months, satellite cells exhibit impaired ability to return to quiescence compared with control cells   (MGI Ref ID J:190460)
    • increased satellite cell number
      • moderate in untreated mice   (MGI Ref ID J:190460)
      • 2.4-fold increase in self-renewed satellite cells following cardiotoxin treatment   (MGI Ref ID J:190460)
      • 2-fold increase in quiescent sublaminar Pax7+ satellite cells following cardiotoxin treatment   (MGI Ref ID J:190460)
      • however, the number of quiescent sublaminar Pax7+ satellite cells is number in untreated mice   (MGI Ref ID J:190460)
View Research Applications

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

Apoptosis Research

Cardiovascular Research
Heart Abnormalities

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Dusp6tm1Jmol
Allele Name targeted mutation 1, Jeffery D Molkentin
Allele Type Targeted (Null/Knockout)
Mutation Made By Jeffery Molkentin,   Cincinnati Children's Hospital
Strain of Origin129
ES Cell Line Strain129
Gene Symbol and Name Dusp6, dual specificity phosphatase 6
Chromosome 10
Gene Common Name(s) 1300019I03Rik; HH19; MKP-3; MKP3; PYST1; RIKEN cDNA 1300019I03 gene;
Molecular Note All 3 exons were replaced with a neo cassette via homologous recombination. Western blot analysis confirmed the absence of protein in the lung, spleen, thymus, and heart of homozygous mice. [MGI Ref ID J:142966]

Genotyping

Genotyping Information

Genotyping Protocols

Dusp6tm1Jmol STD PCR, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Maillet M; Purcell NH; Sargent MA; York AJ; Bueno OF; Molkentin JD. 2008. DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility. J Biol Chem 283(45):31246-55. [PubMed: 18753132]  [MGI Ref ID J:142966]

Additional References

Dusp6tm1Jmol related

Le Grand F; Grifone R; Mourikis P; Houbron C; Gigaud C; Pujol J; Maillet M; Pages G; Rudnicki M; Tajbakhsh S; Maire P. 2012. Six1 regulates stem cell repair potential and self-renewal during skeletal muscle regeneration. J Cell Biol 198(5):815-32. [PubMed: 22945933]  [MGI Ref ID J:190460]

Saha M; Skopelja S; Martinez E; Alvarez DL; Liponis BS; Romero-Sandoval EA. 2013. Spinal mitogen-activated protein kinase phosphatase-3 (MKP-3) is necessary for the normal resolution of mechanical allodynia in a mouse model of acute postoperative pain. J Neurosci 33(43):17182-7. [PubMed: 24155322]  [MGI Ref ID J:204669]

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 maintained as a live colony, homozygotes or heterozygotes may be bred.

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
   101045 B6129SF2/J (approximate)
 
  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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