Cdh5 Knockin mouse models

Vascular endothelial cadherin is encoded by Cdh5, ortholog of human CDH5, a classical cadherin restricted to endothelium whose five extracellular repeats mediate calcium-dependent homophilic adhesion at adherens junctions while the cytoplasmic tail binds p120 catenin to block internalization and beta-catenin to link alpha-catenin and the actin cytoskeleton. VEGF-driven Src and Vav2 phosphorylation of specific tail tyrosines triggers junction disassembly and permeability, making this locus the molecular control point for vascular leak. Germline deletion is lethal near midgestation from failed vascular remodeling rather than failed vasculogenesis, so conditional alleles are mandatory, and phosphosite knockins that lock or mimic tyrosine modification separate adhesion from signaling far better than a null. Because Cdh5-CreERT2 is the field standard pan-endothelial driver, confirm that your floxed allele and driver are not competing at the same locus. Assess Evans blue extravasation, junction morphology by immunofluorescence, and retinal angiogenesis.

An engineered Cdh5 allele can introduce a human coding region, a point change, or a fluorescent reporter without random transgene integration noise.