Wnt5a Conditional Knockout mouse models

Wnt5a, the mouse ortholog of human WNT5A, encodes the prototypical noncanonical Wnt and signals through Frizzled with the alternative receptors ROR2 and RYK to engage VANGL2, Dishevelled, RHOA, ROCK, and JNK, directing planar polarity and convergent extension while frequently antagonizing beta-catenin-dependent transcription in the same tissue. Nulls die perinatally with severe anterior to posterior truncation, shortened limbs and digits, and craniofacial and genital defects, phenocopying the Ror2 mutant and matching human disease, since heterozygous WNT5A mutations cause dominant Robinow syndrome while recessive ROR2 mutations cause the recessive form. Conditional deletion is therefore required for postnatal work in lung, mammary gland, and tumor stroma, patient cysteine substitution knockins test ligand and receptor coupling rather than absence, and humanization supports pathway pharmacology. Wnt11 and Wnt5b provide overlapping polarity input, so compound conditional alleles and a lineage-validated Cre driver protect against under-reading a real requirement.

A floxed Wnt5a allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.