Ablation of Uroplakin III Gene Results in Small Urothelial Plaques, Urothelial Leakage, and Vesicoureteral Reflux

• DOI: 10.1083/jcb.151.5.961
• Publication Date: 2002-07-26T16:46:23Z
• Authors: Ping Hu; Fang-Ming Deng; Feng-Xia Liang; Chuan-Min Hu; Anna B. Auerbach; Ellen Shapiro; Xue-Ru Wu; Bechara Kachar; Tung-Tien Sun
• Keywords: Urothelial Cell

Urothelium synthesizes a group of integral membrane proteins called uroplakins, which form two-dimensional crystals (urothelial plaques) covering >90% the apical urothelial surface. We show that ablation mouse uroplakin III (UPIII) gene leads to overexpression, defective glycosylation, and abnormal targeting Ib, presumed partner UPIII. The UPIII-depleted urothelium features small plaques, becomes leaky, has enlarged ureteral orifices resulting in back flow urine, hydronephrosis, altered renal function indicators. Thus, UPIII is an subunit plaque contributes permeability barrier urothelium, deficiency can lead global anomalies urinary tract. single urothelial-specific therefore cause primary vesicoureteral reflux (VUR), hereditary disease affecting ∼1% pregnancies representing leading failure infants. fact VUR caused by deletion seems distinct from angiotensin receptor II suggests existence subtypes. Mutations multiple gene, including some are specific, may different subtypes reflux. Studies animal models well-defined genetic defects should improved molecular classification, prenatal diagnosis, therapy this important problem.