noninvasive assessment of antenatal hydronephrosis in mice reveals a critical role for robo2 in maintaining anti-reflux mechanism无创性产前评估老鼠肾盂积水robo2揭示了一个重要角色在维持抗反流机制.pdfVIP

Noninvasive Assessment of Antenatal Hydronephrosis in Mice Reveals a Critical Role for Robo2 in Maintaining Anti-Reflux Mechanism 1,3 1,4 1 2 1 1 Hang Wang , Qinggang Li , Juan Liu , Cathy Mendelsohn , David J. Salant , Weining Lu * 1 Renal Section, Department of Medicine, Boston University Medical Center, Boston, Massachusetts, United States of America, 2 Department of Urology, Columbia University, New York, New York, United States of America, 3 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China, 4 Department of Nephrology, PLA General Hospital, Beijing, China Abstract Antenatal hydronephrosis and vesicoureteral reflux (VUR) are common renal tract birth defects. We recently showed that disruption of the Robo2 gene is associated with VUR in humans and antenatal hydronephrosis in knockout mice. However, the natural history, causal relationship and developmental origins of these clinical conditions remain largely unclear. Although the hydronephrosis phenotype in Robo2 knockout mice has been attributed to the coexistence of ureteral reflux and obstruction in the same mice, this hypothesis has not been tested experimentally. Here we used noninvasive high- resolution micro-ultrasonography and pathological analysis to follow the progression of antenatal hydronephrosis in individual Robo2-deficient mice from embryo to adulthood. We found that hydronephrosis progressed continuously after birth with no spontaneous resolution. With the use of a microbubble ultrasound contrast agent and ultrasound-guided percutaneous aspiration, we demonstrated that antenatal hydronephrosis in Robo2-deficient mice is caused by high-grade VUR re