Description

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. Mating System Homozygote x Homozygote         (Female x Male)   24-FEB-11 Species laboratory mouse Generation F?+F5 (26-JAN-11) Generation Definitions   Donating Investigator Jeffery D. Molkentin,   Children's Hospital Medical Center

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 Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Dusp6^tm1Jmol/Dusp6^tm1Jmol

        involves: 129X1/SvJ * 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 (knock-out)
Mutation Made By		Jeffery Molkentin,   Children's Hospital Medical Center
Strain of Origin		129X1/SvJ
ES Cell Line Strain		129
Gene Symbol and Name		Dusp6, dual specificity phosphatase 6
Chromosome		10
Gene Common Name(s)		1300019I03Rik; 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

Dusp6^tm1Jmol 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

Dusp6^tm1Jmol 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]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, homozygotes or heterozygotes may be bred.
Mating System	Homozygote x Homozygote         (Female x Male)   24-FEB-11

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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