Description

Strain Information

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)   02-JUN-06 Species laboratory mouse Generation F?+F14 (30-JUN-11) Generation Definitions   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 Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Epha2^tm1Jrui allele

006070

CBy.129S6(B6)-Epha2tm1Jrui/J

View Strains carrying   Epha2^tm1Jrui     (1 strain)

Strains carrying other alleles of Epha2

006070

CBy.129S6(B6)-Epha2tm1Jrui/J

View Strains carrying other alleles of Epha2     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Epha2^tm1Jrui/Epha2^tm1Jrui

        involves: 129 * BALB/c * C57BL/6

• cardiovascular system phenotype
• abnormal angiogenesis
  • endothelial cells fail to assemble into capillary-like structure (vascular assembly) and to migrate in response to ephrin A1 (Efna1) in vitro   (MGI Ref ID J:89275)
  • mutants show impaired ephrin A1-induced angiogenesis in vivo   (MGI Ref ID J:89275)

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
      tumor immunology
Cardiovascular Research

Genes & Alleles

Gene & Allele Information provided by MGI

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)		ARCC2; AW545284; CTPA; CTPP1; 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

Genotyping Information

Genotyping Protocols

Epha2^tm1Jrui, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Additional References

Epha2^tm1Jrui related

Brantley-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]

Okazaki T; Ni A; Baluk P; Ayeni OA; Kearley J; Coyle AJ; Humbles A; McDonald DM. 2009. Capillary defects and exaggerated inflammatory response in the airways of EphA2-deficient mice. Am J Pathol 174(6):2388-99. [PubMed: 19443703]  [MGI Ref ID J:148922]

Vaught D; Chen J; Brantley-Sieders DM. 2009. Regulation of mammary gland branching morphogenesis by EphA2 receptor tyrosine kinase. Mol Biol Cell 20(10):2572-81. [PubMed: 19321667]  [MGI Ref ID J:175142]

Health & husbandry

Health & Colony Maintenance Information

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)   02-JUN-06
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

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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