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Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Generation ?+F3 (21-AUG-07) Donating Investigator Joseph Ruiz, Indiana University School of Medicine Description
Mice homozygous for this targeted mutation are viable and fertile with no overt developmental or behavioral abnormalities. The Jackson Laboratory is distributing these mice on their original C57BL/6;129S6 mixed background. The published phenotype of these mutant mice is described below.In mutant mice of a mixed BALB/c, C57BL/6, and 129S6 background, murine pulmonary microvascular endothelial cells (MPMEC) isolated from homozygotes express no endogenous protein. MPMEC show impaired ephrin-A1-induced vascular assembly and defective migration both in vitro and in vivo. In addition, MPMEC from homozygous mice exhibit decreased angiogenesis and fail to activate Rac1 in response to ephrin-A1 in vivo. Mutant mice crossed to BALB/c for 7 generations are protected from tumor progression, angiogenesis and metastasis following metastatic mammary adenocarcinoma cell transplantation. These mutant mice may be useful in studies of postnatal angiogenesis (endothelial cell migration, assembly into new tubules, and cytoskeletal regulation), as well as adenocarcinoma and breast cancer research.
Development
A targeting vector was designed to insert a bacterial neo casette into exon 5 (nucleotide 1372, corresponding to amino acid residue 426 in the extracellular domain) of the endogenous gene. This construct was microinjected into 129S6/SvEvTac-derived CCE embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females for one generation. Heterozygous offspring were interbred to produce homozygous mice. Mutant mice were maintained by breeding non-agouti siblings for more than 10 years before arrival at The Jackson Laboratory.
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
Strains carrying Epha2tm1Jrui allele
006070 CBy.129S6(B6)-Epha2tm1Jrui/J View Strains carrying Epha2tm1Jrui (1 strain)
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.
Epha2tm1Jrui/Epha2tm1Jrui
involves: 129 * BALB/c * C57BL/6
- cardiovascular system phenotype
- abnormal angiogenesis (MGI Ref ID J:89275)
- attenuated angiogenic response to ephrin A1
- angiogenesis was normal during embryogenesis
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Cancer Research
Other (tumor metastasis)
Tumor Resistance
Tumor Suppressor Genes
Cardiovascular Research
Other
Vascular Defects
Research Tools
Cancer Research (anti-tumor activity)
Cancer Research (tumor immunology)
Cardiovascular Research
| Allele Symbol | Epha2tm1Jrui | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Joseph C Ruiz | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Epha2-; Epha2tm1Jinc; | ||
| Mutation Made By | Joseph Ruiz, Indiana University School of Medicine | ||
| Gene Symbol and Name | Epha2, Eph receptor A2 | ||
| Chromosome | 4 | ||
| Gene Common Name(s) | AW545284; ECK; Eck; Myk2; Sek-2; Sek2; epithelial cell kinase; expressed sequence AW545284; | ||
| Molecular Note | A neo cassette was inserted at nucleotide 1372, within the sequence encoding the extracellular domain. Although the resultant transcript putatively encodes a nonfunctional protein truncated at amino acid 426, no protein was detected by Western blot analysis of murine pulmonary microvascular endothelial cells from mutant mice. [MGI Ref ID J:89275] | ||
Genotyping Protocols
Epha2tm1Jrui, SEP PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Brantley-Sieders DM; Caughron J; Hicks D; Pozzi A; Ruiz JC; Chen J. 2004. EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation. J Cell Sci 117(Pt 10):2037-49. [PubMed: 15054110] [MGI Ref ID J:89275]
Epha2tm1Jrui relatedBrantley-Sieders DM; Fang WB; Hicks DJ; Zhuang G; Shyr Y; Chen J. 2005. Impaired tumor microenvironment in EphA2-deficient mice inhibits tumor angiogenesis and metastatic progression. FASEB J 19(13):1884-6. [PubMed: 16166198] [MGI Ref ID J:102664]
Brantley-Sieders DM; Zhuang G; Hicks D; Fang WB; Hwang Y; Cates JM; Coffman K; Jackson D; Bruckheimer E; Muraoka-Cook RS; Chen J. 2008. The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling. J Clin Invest 118(1):64-78. [PubMed: 18079969] [MGI Ref ID J:130805]
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice are bred. Mating System Homozygote x Homozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $155.60 Female or Male Homozygous for Epha2tm1Jrui *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $311.20 Homozygous for Epha2tm1Jrui x Homozygous for Epha2tm1Jrui
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $202.30 Female or Male Homozygous for Epha2tm1Jrui *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $404.60 Homozygous for Epha2tm1Jrui x Homozygous for Epha2tm1Jrui
| Supply Notes |
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| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| 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. | ||
Purchasing Information
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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