Mechanisms of disease: What can mouse models tell us about the molecular processes underlying Dent disease?

Sandra E. Guggino

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)449-455
Number of pages7
JournalNature Clinical Practice Nephrology
Issue number8
StatePublished - Aug 2007


  • Citrate therapy
  • ClC-5
  • Hypercalciuria
  • Receptor-mediated endocytosis
  • Renal failure

ASJC Scopus subject areas

  • Nephrology


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