EphB4 (Ephrin receptor B4) KinaseSwitch mouse

Model Description

• The EphB4 receptor binds the ligand EphrinB2. Activation and signalling through the receptor is important during vascular development. The EphB4 (Eph receptor B4 tyrosine kinase) KinaseSwitch mouse strain carries point mutations at the genomic level at position T693 in the ATP binding pocket of the EphB4 kinase domain (EphB4T693A). The mutation switches the gatekeeper residue at Threonine 693 to Alanine. Insertion of this point mutation into EphB4 will not affect protein expression or protein stability of the kinase. Enzymatic activity of EphB4T693A is not affected compared to the WT kinase when analyzed using in vitro kinase assays. However, mutation of residue T693A allows the inducible inhibition of EphB4 kinase activity after treatment of homozygous mutant EphB4T693A animals with a proprietary, pharmacological inhibitor (NaPP1). The inhibitor is specifically designed to recognize the EphB4T693A allele. Inhibition by NaPP1 is therefore selective for EphB4 and mimics the action of a drug against this specific kinase isoform. Homozygous mutant animals can be treated with the inhibitor at any time during animal development leading to loss of kinase activity. The inhibitor penetrates the blood-brain and blood-testis barriers.
• Some relevant applications include studies in neuroscience, angiogenesis and oncology.

Origin:
The EphB4 KinaseSwitch mouse strain was generated by Cellular Genomics Inc. using C57BL/6 ES cells. Gene targeting in ES cells was used to insert the T693A point mutation into the mouse genome. Targeted ES cells were validated and used for mouse production using standard techniques. The line was cryopreserved as heterozygote embryos. When Taconic acquired the exclusive rights to the KinaseSwitch technology from Princeton University, cryopreserved embryos were transferred to Taconic for rederivation via embryo transfer. The mouse line has been intercrossed to homozygosity and is maintained as a homozygous colony.

Color: Black

Animal Diet: NIH #31M Rodent Diet

Licensing Requirements:
Access to this model requires execution of an agreement and cryorecovery services to recover the line. Non-profit users may execute a Limited Breeding Agreement which currently carries a fee of $2,500/year. This line is offered for contract production to for-profit users. For-profit users must sign a license agreement which currently carries a fee of $5,000/year. Cryorecovery and contract production fees are additional.

Availability: This model is available for immediate cryorecovery.

Price Table

7742 (in U.S. Dollars)

Contact Us or call:

• 888.TACONIC (822.6642)
• Fax: 518.697.3910
• +45 70 23 04 05 (Europe)