Strain Name:

B6.129S-Runx1tm1Spe/J

Stock Number:

005669

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Availability:

Cryopreserved - Ready for recovery

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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 Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating System+/+ sibling x Heterozygote         (Female x Male)   05-OCT-06
Specieslaboratory mouse
GenerationN5p
Generation Definitions
 
Donating Investigator Nancy Speck,   University of Pennsylvania

Description
Heterozygous mice are viable, fertile, devoid of hemorrhagic lesions, and exhibit mild hematopoietic impairment. Mice that are homozygous for the targeted mutation have an embryonic lethal phenotype; animals are alive at embryonic day 11.5, but start dying at embryonic day 12.5. Embryos exhibit extensive hemorrhagic lesions in the central nervous system including the intraventricular regions and metencephalon as well as segmental bleeds at the VII-VIII cranial nerve complex, cervical, thoracic, and caudal regions. At embryonic day 10.5, symmetrical and bilateral necrosis preceding hemorrhage is observed in homozygotes. Homozygous disruption of the endogenous gene completely blocks definitive erythropoiesis, myelopoiesis, and lymphopoiesis. This mutant may be useful in leukemia studies as disruption of the human homolog of this gene is associated with many different leukemias.

Development
A targeting vector containing a phosphoglycerol kinase-driven neomycin resistance gene disrupted the 3.2 kb region coding for amino acids 143-178 (the final 35 amino acids in the DNA binding domain) of the endogenous gene. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were backcrossed to C57BL/6J females. Heterozygotes were backcrossed to (129S1/SvImJ x C57BL/6J)F1 mice for more than 10 generations and then backcrossed to C57BL/6J for at least five more generations.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Runx1
008772   B6.129P2-Runx1tm1Tani/J
010673   B6;129-Runx1tm3.1Spe/J
View Strains carrying other alleles of Runx1     (2 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.
Platelet Disorder, Familial, with Associated Myeloid Malignancy; FPDMM   (RUNX1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Runx1tm1Spe/Runx1+

        either: (involves: 129S4/SvJae * BALB/c * C57BL/6 * CBA/Ca) or (involves: 129S4/SvJae * C57BL/6 * CBA/Ca)
  • tumorigenesis
  • increased T cell derived lymphoma incidence
    • survival of mutants shows slight but significant increase compared to transgenic mice on a wild-type Runx1 background   (MGI Ref ID J:80829)

Runx1tm1Spe/Runx1+

        either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)
  • tumorigenesis
  • *normal* tumorigenesis
    • mice infected with Moloney murine leukemia virus within 24 hours of birth do not show any increase in tumor incidence or latency compared to infected littermate controls   (MGI Ref ID J:80829)
  • embryogenesis phenotype
  • abnormal embryonic hematopoiesis
    • at E11.5, animals have a >3-fold decrease in CFU-C in AGM (aorta/gonad/mesonephros) regions than wild-type embryos in the AGM region   (MGI Ref ID J:120100)
  • hematopoietic system phenotype
  • abnormal embryonic hematopoiesis
    • at E11.5, animals have a >3-fold decrease in CFU-C in AGM (aorta/gonad/mesonephros) regions than wild-type embryos in the AGM region   (MGI Ref ID J:120100)
  • decreased CD4-positive T cell number
    • a significant decrease in percentage of CD4+ splenic T cells and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed   (MGI Ref ID J:120100)
  • immune system phenotype
  • decreased CD4-positive T cell number
    • a significant decrease in percentage of CD4+ splenic T cells and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed   (MGI Ref ID J:120100)

Runx1tm1Spe/Runx1tm1Spe

        either: (involves: 129S4/Jae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)
  • mortality/aging
  • complete embryonic lethality during organogenesis
    • die between E11.5 and E12.5   (MGI Ref ID J:35115)
  • cardiovascular system phenotype
  • hemorrhage
    • extensive hemorrhages, with 14% of homozygotes showing hemorrhaging at E10.5, 73% at E11.5 and 100% at E12.5   (MGI Ref ID J:35115)
    • internal hemorrhage
      • most extensive hemorrhages involve the central nervous system and are located in the isthmus, ventral metencephalon, and spinal cord   (MGI Ref ID J:35115)
      • focal petechial hemorrhages are seen in peripheral nerves and intersegmental regions, especially prominent at the nerve roots of VII-VIII cranial nerve complex and at some spinal nerves   (MGI Ref ID J:35115)
      • mesodermal petechial hemorrhages are seen in a small number of embryos   (MGI Ref ID J:35115)
      • hemopericardium
        • pericardiac and peritoneal hemorrhages are seen in some embryos   (MGI Ref ID J:35115)
  • hematopoietic system phenotype
  • abnormal erythropoiesis
    • only primitive nucleated erythroid cells are seen in liver sections or smears at E11 and E12.5, respectively, indicating a block in definitive erythropoiesis   (MGI Ref ID J:35115)
    • no erythroid colonies differentiate from yolk sac cells as in wild-type   (MGI Ref ID J:35115)
    • increased nucleated erythrocyte cell number
      • only primitive nucleated erythroid cells are seen in liver sections or smears at E11 and E12.5, respectively, indicating a block in definitive erythropoiesis   (MGI Ref ID J:35115)
  • impaired hematopoiesis
    • fetal liver hematopoiesis is impaired, however primitive erythrocytes are normal   (MGI Ref ID J:35115)
  • impaired myelopoiesis
    • no myeloid colonies differentiate from yolk sac cells as in wild-type   (MGI Ref ID J:35115)
  • cellular phenotype
  • necrosis
    • foci of cellular necrosis, often bilateral and symmetrical, are seen at the nerve/CNS interfaces of cranial and spinal nerves at E10.5   (MGI Ref ID J:35115)
    • somitic/intersomitic necrosis is seen in the lower thoracic and lumbar regions   (MGI Ref ID J:35115)
  • immune system phenotype
  • impaired myelopoiesis
    • no myeloid colonies differentiate from yolk sac cells as in wild-type   (MGI Ref ID J:35115)
  • homeostasis/metabolism phenotype
  • hemopericardium
    • pericardiac and peritoneal hemorrhages are seen in some embryos   (MGI Ref ID J:35115)
View Research Applications

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

Cardiovascular Research
Vascular Defects
      defective leukocyte function

Developmental Biology Research
Embryonic Lethality (Homozygous)
Internal/Organ Defects
      hematopoietic defects
Lymphoid Tissue Defects
      hematopoietic defects

Hematological Research
Hematopoietic Defects
Immunological Defects

Immunology, Inflammation and Autoimmunity Research
Lymphoid Tissue Defects
      hematopoietic development

Internal/Organ Research
Liver Defects

Research Tools
Cancer Research
      Leukemia
Hematological Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Runx1tm1Spe
Allele Name targeted mutation 1, Nancy A Speck
Allele Type Targeted (Null/Knockout)
Common Name(s) Cbfa2-; Cbfa2rd; Runx1-; Runx1deltaE4; Runx1rd;
Mutation Made By Nancy Speck,   University of Pennsylvania
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Runx1, runt related transcription factor 1
Chromosome 16
Gene Common Name(s) AI462102; AML1; AML1-EVI-1; AMLCR1; CBFA2; Cbfa2; EVI-1; PEBP2aB; Pebp2a2; core binding factor alpha 2; expressed sequence AI462102; runt domain, alpha subunit 2;
Molecular Note Exon 4, which encodes a portion of the DNA-binding domain, was replaced with a PGK-neo cassette. RT-PCR analysis showed a lack of normal transcript in homozygous mutant mice. [MGI Ref ID J:35115]

Genotyping

Genotyping Information

Genotyping Protocols

Runx1tm1Spe, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Wang Q; Stacy T; Binder M; Marin-Padilla M; Sharpe AH; Speck NA. 1996. Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc Natl Acad Sci U S A 93(8):3444-9. [PubMed: 8622955]  [MGI Ref ID J:35115]

Additional References

Runx1tm1Spe related

Bee T; Swiers G; Muroi S; Pozner A; Nottingham W; Santos AC; Li PS; Taniuchi I; de Bruijn MF. 2010. Nonredundant roles for Runx1 alternative promoters reflect their activity at discrete stages of developmental hematopoiesis. Blood 115(15):3042-50. [PubMed: 20139099]  [MGI Ref ID J:160791]

Ferreras C; Lancrin C; Lie-A-Ling M; Kouskoff V; Lacaud G. 2011. Identification and characterization of a novel transcriptional target of RUNX1/AML1 at the onset of hematopoietic development. Blood 118(3):594-7. [PubMed: 21498670]  [MGI Ref ID J:174907]

Kundu M; Compton S; Garrett-Beal L; Stacy T; Starost MF; Eckhaus M; Speck NA; Liu PP. 2005. Runx1 deficiency predisposes mice to T-lymphoblastic lymphoma. Blood 106(10):3621-4. [PubMed: 16051740]  [MGI Ref ID J:106809]

Matheny CJ; Speck ME; Cushing PR; Zhou Y; Corpora T; Regan M; Newman M; Roudaia L; Speck CL; Gu TL; Griffey SM; Bushweller JH; Speck NA. 2007. Disease mutations in RUNX1 and RUNX2 create nonfunctional, dominant-negative, or hypomorphic alleles. EMBO J 26(4):1163-75. [PubMed: 17290219]  [MGI Ref ID J:120100]

Mizuochi C; Fraser ST; Biasch K; Horio Y; Kikushige Y; Tani K; Akashi K; Tavian M; Sugiyama D. 2012. Intra-aortic clusters undergo endothelial to hematopoietic phenotypic transition during early embryogenesis. PLoS One 7(4):e35763. [PubMed: 22558218]  [MGI Ref ID J:187282]

North T; Gu TL; Stacy T; Wang Q; Howard L; Binder M; Marin-Padilla M; Speck NA. 1999. Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. Development 126(11):2563-75. [PubMed: 10226014]  [MGI Ref ID J:56184]

Rhodes KE; Gekas C; Wang Y; Lux CT; Francis CS; Chan DN; Conway S; Orkin SH; Yoder MC; Mikkola HK. 2008. The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation. Cell Stem Cell 2(3):252-63. [PubMed: 18371450]  [MGI Ref ID J:149803]

Theriault FM; Nuthall HN; Dong Z; Lo R; Barnabe-Heider F; Miller FD; Stifani S. 2005. Role for Runx1 in the proliferation and neuronal differentiation of selected progenitor cells in the mammalian nervous system. J Neurosci 25(8):2050-61. [PubMed: 15728845]  [MGI Ref ID J:97371]

Vaillant F; Blyth K; Andrew L; Neil JC; Cameron ER. 2002. Enforced Expression of Runx2 Perturbs T Cell Development at a Stage Coincident with beta-Selection. J Immunol 169(6):2866-74. [PubMed: 12218099]  [MGI Ref ID J:79075]

Woolf E; Xiao C; Fainaru O; Lotem J; Rosen D; Negreanu V; Bernstein Y; Goldenberg D; Brenner O; Berke G; Levanon D; Groner Y. 2003. Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis. Proc Natl Acad Sci U S A 100(13):7731-6. [PubMed: 12796513]  [MGI Ref ID J:84629]

Wotton S; Stewart M; Blyth K; Vaillant F; Kilbey A; Neil JC; Cameron ER. 2002. Proviral Insertion Indicates a Dominant Oncogenic Role for Runx1/AML-1 in T-Cell Lymphoma. Cancer Res 62(24):7181-5. [PubMed: 12499254]  [MGI Ref ID J:80829]

Yokomizo T; Dzierzak E. 2010. Three-dimensional cartography of hematopoietic clusters in the vasculature of whole mouse embryos. Development 137(21):3651-61. [PubMed: 20876651]  [MGI Ref ID J:165571]

Zeigler BM; Sugiyama D; Chen M; Guo Y; Downs KM; Speck NA. 2006. The allantois and chorion, when isolated before circulation or chorio-allantoic fusion, have hematopoietic potential. Development 133(21):4183-92. [PubMed: 17038514]  [MGI Ref ID J:114096]

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, these mice are maintained as heterozygotes. Homozygotes are embryonic lethal.
Mating System+/+ sibling x Heterozygote         (Female x Male)   05-OCT-06

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* $2525.00
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 willfulfill 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* $3283.00
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 willfulfill 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
   Wild-type from the colony
   000664 C57BL/6J
 
  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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