Decreased Apoptosis and Persistence of the Common Nephric Duct During the Development of an Aberrant Vesicoureteral Junction in Dlg1 Gene‐Targeted Mice

ABSTRACT Congenital anomalies of the kidney and urinary tract occur at a frequency of 1 in 500 live births in humans. Mutant mice null for Dlg1 (Dlg1−/− mice), a membrane‐associated guanylate kinase containing PDZ domains, exhibit various urogenital malformations, including hypoplasia of the kidney and ureter, megaureter, hydronephrosis, and aplasia of the seminal vesicle and the vagina. The common nephric duct (CND) is a distal part of the Wolffian duct between the ureteric branch and the opening to the urogenital sinus, and normally disappears by embryonic day (E) 12.5 by a downward shift of the ureteric branch. Although retardation of the disappearance of the CND is apparent during urogenital development in Dlg1−/− mice, its pathogenesis and prognosis are unclear. In the present study, we found a decrease in apoptotic cells in the CND epithelium in Dlg1−/− mice at E11.5. Cell proliferation did not change. Additionally, histological observation of the development of the ureteral orifice indicated that the CND remained at E15.5 and was widely open to the vesical lumen in Dlg1−/− mice, in contrast to the complete disappearance of the CND and a narrow ureteric orifice in control mice. The dilatation of the vesicoureteral junction remained at E18.5. Opening of the vesicoureteral junction is known to cause vesicoureteral reflux and subsequent megaureter and hydronephrosis. Therefore, our present observation demonstrates that lack of the Dlg1 gene induces a decr...
Source: The Anatomical Record Part B: The New Anatomist - Category: Anatomy Authors: Tags: Full Length Article Source Type: research