Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis

Sandra J. Engle, Michael G. Stockelman, Ju Chen, Greg Boivin, Moo Nahm Yum, Philip M. Davies, Mo Yin Ying, Amrik Sahota, H. Anne Simmonds, Peter J. Stambrook, Jay A. Tischfield

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Adenine phosphoribosyltransferase (APRT) deficiency in humans is an autosomal recessive syndrome characterized by the urinary excretion of adenine and the highly insoluble compound 2,8-dihydroxyadenine (DHA) that can produce kidney stones or renal failure. Targeted homologous recombination in embryonic stem cells was used to produce mice that lack APRT. Mice homozygous for a null Aprt allele excrete adenine and DHA crystals in the urine. Renal histopathology showed extensive tubular dilation, inflammation, necrosis, and fibrosis that varied in severity between different mouse backgrounds. Thus, biochemical and histological changes in these mice mimic the human disease and provide a suitable model of human hereditary nephrolithiasis.

Original languageEnglish (US)
Pages (from-to)5307-5312
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number11
DOIs
StatePublished - May 28 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Gene targeting
  • Mouse model
  • Purine metabolism
  • Renal disease

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