Null mutations of Tshz3 in mice lead to disorganized mesenchymal cells and missing expression of the SM marker α-SMA in the proximal ureter, defective ureteric contractility, and a prominent proximal hydroureter and hydronephrosis, a fully penetrant bilateral phenotype affecting both sexes, reminiscent of human congenital ureteropelvic junction obstruction [20] (Supplementary Fig. 3). Here, ACTA1 is linked to hydronephrosis.