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Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Heterozygote (Female x Male) Species laboratory mouse Generation N5p Donating Investigator Nancy Speck, Dartmouth Medical School 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 | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Congenic Nomenclature
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from 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
- T cell derived lymphoma (MGI Ref ID J:80829)
- survival of mutants shows slight but significant increase compared to transgenic mice on a wild-type Runx1 background
Runx1tm1Spe/Runx1+
either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)
- tumorigenesis
- *normal* tumorigenesis (MGI Ref ID J:80829)
- 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
- embryogenesis phenotype
- abnormal embryonic hematopoiesis (MGI Ref ID J:120100)
- 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
- hematopoietic system phenotype
- abnormal embryonic hematopoiesis (MGI Ref ID J:120100)
- 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
- decreased CD4-positive T cell number (MGI Ref ID J:120100)
- 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
- immune system phenotype
- decreased CD4-positive T cell number (MGI Ref ID J:120100)
- 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
Runx1tm1Spe/Runx1tm1Spe
either: (involves: 129S4/Jae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)
- lethality-prenatal/perinatal
- embryonic lethality during organogenesis (MGI Ref ID J:35115)
- die between E11.5 and E12.5
- cardiovascular system phenotype
- hemorrhage (MGI Ref ID J:35115)
- extensive hemorrhages, with 14% of homozygotes showing hemorrhaging at E10.5, 73% at E11.5 and 100% at E12.5
- internal hemorrhage (MGI Ref ID J:35115)
- most extensive hemorrhages involve the central nervous system and are located in the isthmus, ventral metencephalon, and spinal cord
- 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
- mesodermal petechial hemorrhages are seen in a small number of embryos
- hemopericardium (MGI Ref ID J:35115)
- pericardiac and peritoneal hemorrhages are seen in some embryos
- hematopoietic system phenotype
- abnormal erythropoiesis (MGI Ref ID J:35115)
- only primitive nucleated erythroid cells are seen in liver sections or smears at E11 and E12.5, respectively, indicating a block in definitive erythropoiesis
- no erythroid colonies differentiate from yolk sac cells as in wild-type
- impaired hematopoiesis (MGI Ref ID J:35115)
- fetal liver hematopoiesis is impaired, however primitive erythrocytes are normal
- impaired myelopoiesis (MGI Ref ID J:35115)
- no myeloid colonies differentiate from yolk sac cells as in wild-type
- cellular phenotype
- necrosis (MGI Ref ID J:35115)
- foci of cellular necrosis, often bilateral and symmetrical, are seen at the nerve/CNS interfaces of cranial and spinal nerves at E10.5
- somitic/intersomitic necrosis is seen in the lower thoracic and lumbar regions
- immune system phenotype
- impaired myelopoiesis (MGI Ref ID J:35115)
- no myeloid colonies differentiate from yolk sac cells as in wild-type
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 and Inflammation Research
Lymphoid Tissue Defects (hematopoietic development)
Internal/Organ Research
Liver Defects
Research Tools
Cancer Research (Leukemia)
Hematological Research
| Allele Symbol | Runx1tm1Spe | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Nancy A Speck | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Cbfa2-; Cbfa2rd; Runx1-; Runx1deltaE4; Runx1rd; | ||
| Mutation Made By | Nancy Speck, Dartmouth Medical School | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/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 deleted by the insertion of a PGK-neo cassette. RT-PCR analysis showed a lack of normal transcript in homozygous mutant mice. [MGI Ref ID J:35115] | ||
Genotyping Protocols
Runx1tm1Spe, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
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]
Runx1tm1Spe relatedKundu 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]
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]
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]
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]
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are maintained as heterozygotes. Homozygotes are embryonic lethal. Mating System +/+ sibling x Heterozygote (Female x Male)
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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