Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases.

The apical surface of mouse urothelium is covered by two-dimensional crystals (plaques) of uroplakin (UP) particles. To study uroplakin function, we ablated the mouse UPII gene. A comparison of the phenotypes of UPII- and UPIII-deficient mice yielded new insights into the mechanism of plaque formation and some fundamental features of urothelial differentiation. Although UPIII knockout yielded small plaques, UPII knockout abolished plaque formation, indicating that both uroplakin heterodimers (UPIa/II and UPIb/III or IIIb) are required for plaque assembly. Both knockouts had elevated UPIb gene expression, suggesting that this is a general response to defective plaque assembly. Both knockouts also had small superficial cells, suggesting that continued fusion of uroplakin-delivering vesicles with the apical surface may contribute to umbrella cell enlargement. Both knockouts experienced vesicoureteral reflux, hydronephrosis, renal dysfunction, and, in the offspring of some breeding pairs, renal failure and neonatal death. These results highlight the functional importance of uroplakins and establish uroplakin defects as a possible cause of major urinary tract anomalies and death.

Assessment of vasculature using combined MRI and MR angiography.

OBJECTIVE: The purpose of this study was to compare combined cine gradient-recalled echo MRI and MR angiography with conventional angiography in the evaluation of the pulmonary vascular supply in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. MATERIALS AND METHODS: Eleven patients who underwent both MRI and conventional angiography were retrospectively reviewed. Contiguous 2D cine gradient-recalled echo images (TR range/TE, 30-80/4.8; flip angle, 20 degrees or 30 degrees ) and 3D MR angiographic images (TR range/TE range, 3.8-5.0/1.3-2.0; acquisition time, 13-32 sec) using gadopentetate meglumine (0.1-0.2 mmol/kg) were obtained. The presence, size, and course of the pulmonary arteries (main, right, left) and major aortopulmonary collateral arteries (>/= 5 mm) were determined. Presence of minor collateral arteries (< 5 mm) was also noted. Results were compared with findings at conventional angiography. RESULTS: MRI showed all main (n = 4) and branch (n = 17) pulmonary arteries found at conventional angiography and showed the pulmonary confluence in five of six cases. MRI showed all major aortic collaterals (n = 22) with a highly significant correlation between MRI and conventional angiography measurements (r = 0.84, p < 0.001 [95% confidence interval, -0.35 to 0.40]). One coronary artery collateral was not shown on MRI examination. At MRI, 12 of 14 major and four of seven minor brachiocephalic artery collaterals were shown. MRI showed more minor aortic collaterals than angiography (22 vs 18 vessels, respectively). CONCLUSION: Combined cine gradient-recalled echo MRI and MR angiography is a reliable method for imaging pulmonary vascular supply in patients with these disorders. Additional prospective studies comparing MRI and conventional angiography may determine whether routine preoperative conventional angiography is required.