B6;129S6-Epha2^tm1Jrui/J

Stock number: 006028
Product name: Epha2-
Research areas: Cancer Research, Cardiovascular Research, Research Tools

Description

This Epha2 knock-out strain may be useful in studies of postnatal angiogenesis, as well as adenocarcinoma and breast cancer research.

Detailed description

Murine pulmonary microvascular endothelial cells (MPMEC) isolated from homozygous mutant mice express no endogenous EPHA2 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 have been shown to exhibit protection from tumor progression, angiogenesis and metastasis following metastatic mammary adenocarcinoma cell transplantation.

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. They may be useful in studies related to 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.

Allele

Symbol: Epha2^tm1Jrui
Name: targeted mutation 1, Joseph C Ruiz
MGI accession ID: MGI:3040415
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Epha2
Marker name: Eph receptor A2
Chromosome: 4
Strain of origin: 129S/SvEv-Gpi1^c
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.