Jacob Vinitha A, Harbaugh Calista M, Dietz John R, Fenton Robert A, Kim Soo M, Castrop Hayo, Schnermann Jurgen, Knepper Mark A, Chou Chung-Lin, Anderson Stasia A
Laboratory of Kidney and Electrolyte Metabolism, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1603, USA.
Kidney Int. 2008 Nov;74(9):1202-8. doi: 10.1038/ki.2008.392. Epub 2008 Aug 13.
Many transgenic and knockout mice with increased urine flow have structural abnormalities of the renal pelvis and inner medulla. Here, we used high resolution contrast enhanced T1-weighted magnetic resonance imaging of mice whose urea transporters UT-A1 and UT-A3 were deleted (UT-A1/3(-/-) mice) as a model for the in vivo study of such abnormalities. Three distinct variations in the appearance of the renal pelvis were found. These included normal kidneys with no accumulation of contrast agent in the renal pelvis; infrequent frank right-sided unilateral hydronephrosis with marked atrophy of the renal medulla; and a renal pelvic reflux pattern characterized by the presence of contrast agent in the renal pelvis surrounding the renal inner medulla but no substantial atrophy of the medulla. This last pattern was found in most of the advanced age UT-A1/3(-/-) mice and in aquaporin-1 knockout mice. The UT-A1/3(-/-) mice also had increased mean arterial blood pressures. Feeding the mice a low protein diet did not prevent development of their renal pelvic abnormalities. Our studies show that real time imaging of renal pelvic structure in genetically manipulated mice provides a tool for the non-destructive, temporal evaluation of kidney structure.
许多尿流量增加的转基因和基因敲除小鼠存在肾盂和肾内髓质的结构异常。在此,我们使用尿素转运体UT - A1和UT - A3缺失的小鼠(UT - A1/3(-/-)小鼠)的高分辨率对比增强T1加权磁共振成像作为体内研究此类异常的模型。发现肾盂外观有三种不同变化。这些包括肾盂中无造影剂积聚的正常肾脏;罕见的右侧明显单侧肾积水伴肾髓质显著萎缩;以及一种肾盂反流模式,其特征是肾内髓质周围的肾盂中有造影剂,但髓质无实质性萎缩。最后这种模式在大多数老年UT - A1/3(-/-)小鼠和水通道蛋白-1基因敲除小鼠中发现。UT - A1/3(-/-)小鼠的平均动脉血压也升高。给小鼠喂食低蛋白饮食并不能预防其肾盂异常的发展。我们的研究表明,对基因操作小鼠的肾盂结构进行实时成像为肾脏结构的非破坏性、动态评估提供了一种工具。