Wnt4 Conditional Knockout mouse models

Wnt4 is the mouse ortholog of human WNT4 and encodes a ligand operating in both canonical and noncanonical modes, whose defining role is enforcing the ovarian program, since with RSPO1 it sustains beta-catenin in the XX gonad to suppress SOX9 and FGF9, while it also drives Mullerian duct development, adrenal cortex organization, and the mesenchymal to epithelial transition of pretubular aggregates in the nephron lineage. Nulls die perinatally with renal agenesis and partial XX masculinization, human loss of function causes SERKAL syndrome with female to male sex reversal plus renal, adrenal, and pulmonary dysgenesis, and heterozygous variants appear in Mullerian aplasia. Conditional deletion with Sf1-Cre for gonad and adrenal or Six2-Cre and Pax2-Cre for nephron progenitors separates these requirements, and SERKAL knockins test residual activity. Wnt9b overlaps in duct elongation, so compound alleles matter when urogenital tract endpoints, rather than gonadal fate, are primary.

A floxed Wnt4 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.