Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenesis.

Abstract ICAT, inhibitor of β-catenin and T cell factor, or Ctnnbip1, is a negative regulator of the Wnt signaling pathway that interferes with the interaction between β-catenin and T cell factor. Some ICAT-deficient (ICAT −/− ) embryos exhibit unilateral or bilateral renal agenesis. In this study, we investigated developmental processes in the ICAT −/− kidney. ICAT was highly expressed in both the ureteric bud (UB) and the surrounding metanephric mesenchymal (MM) cells in the metanephros of embryonic day E11.5–E13.5 wild-type (ICAT +/+ ) mouse. In the E12.5-ICAT −/− metanephros, UB branching was delayed, and a T-shaped, bifurcated UB was frequently seen; this was never seen in the E12.5-ICAT +/+ metanephros. More apoptotic MM cells were detected in the ICAT −/− metanephros than in the ICAT +/+ metanephros. These results suggest that the loss of ICAT gene function causes the arrest of UB branching and the apoptotic death of MM cells, resulting in renal agenesis.