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dc.contributor.authorWang, Hangen_US
dc.contributor.authorLi, Qinggangen_US
dc.contributor.authorLiu, Juanen_US
dc.contributor.authorMendelsohn, Cathyen_US
dc.contributor.authorSalant, David J.en_US
dc.contributor.authorLu, Weiningen_US
dc.date.accessioned2012-11-07T20:16:00Z
dc.date.available2012-11-07T20:16:00Z
dc.date.issued2011-09-20
dc.identifier.citationWang H, Li Q, Liu J, Mendelsohn C, Salant DJ, et al. (2011) Noninvasive Assessment of Antenatal Hydronephrosis in Mice Reveals a Critical Role for Robo2 in Maintaining Anti-Reflux Mechanism. PLoS ONE 6(9): e24763. doi:10.1371/journal.pone.0024763
dc.identifier.otherdoi:10.1371/journal.pone.0024763
dc.identifier.urihttps://hdl.handle.net/2144/4363
dc.description.abstractAntenatal 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 resulting from a dilated and incompetent ureterovesical junction rather than ureteral obstruction. We further documented Robo2 expression around the developing ureterovesical junction and identified early dilatation of ureteral orifice structures as a potential fetal origin of antenatal hydronephrosis and VUR. Our results thus demonstrate that Robo2 is crucial for the formation of a normal ureteral orifice and for the maintenance of an effective anti-reflux mechanism. This study also establishes a reproducible genetic mouse model of progressive antenatal hydronephrosis and primary high- grade VUR.en_US
dc.description.sponsorshipThis work was supported by National Institutes of Health grants R01DK078226 (to WL), a subcontract of R01HD060050 (to WL), and was also supported in part by Research Grant #6-FY08-34 from the March of Dimes Foundation (to WL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.en_US
dc.language.isoen_US
dc.publisherPLoS ONEen_US
dc.rightsAttribution 3.0 Unporteden_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.titleNoninvasive Assessment of Antenatal Hydronephrosis in Mice Reveals a Critical Role for Robo2 in Maintaining Anti-Reflux Mechanismen_US
dc.typeArticleen_US


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