Guggino Sandra E
Johns Hopkins University Medical School, Baltimore, MD 21205, USA.
Nat Clin Pract Nephrol. 2007 Aug;3(8):449-55. doi: 10.1038/ncpneph0541.
Two knockout mouse models of Dent disease are similar with regard to the characteristics of Fanconi syndrome, but differ markedly with respect to vitamin D and renal calcium handling. One model exhibits hypercalciuria, renal calcifications and renal failure; the other does not. Data from such experimental models have greatly advanced our understanding of the molecular mechanisms underlying Dent disease. This Review summarizes some of the important phenotypic characteristics shared by mouse models and people with Dent disease. Experimental data are used to predict the molecular mechanisms underlying this disease. Receptor-mediated endocytosis and the mistargeting of megalin, cubilin, the sodium/proton exchanger Nhe3 and the sodium/phosphate transporter Napi-2a will be reviewed, and the causes of mistargeting will be discussed. Kidney stones and renal failure are prominent features of Dent disease. Investigations using a mouse model with nephrocalcinosis and renal failure indicate that citrate therapy delays the onset of these processes in Dent disease. Throughout this Review, questions that might underpin new areas of investigation are proposed.
两种丹特病基因敲除小鼠模型在范科尼综合征特征方面相似，但在维生素D和肾脏钙处理方面有显著差异。一种模型表现为高钙尿症、肾钙化和肾衰竭；另一种则没有。来自此类实验模型的数据极大地推进了我们对丹特病潜在分子机制的理解。本综述总结了小鼠模型和丹特病患者共有的一些重要表型特征。实验数据用于预测该疾病的潜在分子机制。将对受体介导的内吞作用以及巨膜蛋白、立方蛋白、钠/质子交换体Nhe3和钠/磷酸盐转运体Napi-2a的靶向错误进行综述，并讨论靶向错误的原因。肾结石和肾衰竭是丹特病的突出特征。使用患有肾钙质沉着症和肾衰竭的小鼠模型进行的研究表明，柠檬酸盐疗法可延缓丹特病中这些过程的发生。在本综述中，还提出了可能为新研究领域提供基础的问题。
