Uric acid stones in the urinary bladder of aryl hydrocarbon receptor (AhR) knockout mice

Ryan Butler, Jose Inzunza, Hitoshi Suzuki, Yoshiaki Fujii-Kuriyama, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The aryl hydrocarbon receptor (AhR) knockout mice raised in the laboratory of Fujii-Kuriyama have been under investigation for several years because of the presence in their urinary bladder of large, yellowish stones. The stones are composed of uric acid and become apparent in the bladders as tiny stones when mice are 10 wk of age. By the time the mice are 6 mo of age, there are usually two or three stones with diameters of 3-4 mm. The urate concentration in the serum was normal but in the urine the concentration was 40-50 mg/dL, which is 10 times higher than that in the WT littermates. There were no apparent histological pathologies in the kidney or joints and the levels of enzymes involved in elimination of purines were normal. The source of the uric acid was therefore judged to be from degradation of nucleic acids due to a high turnover of cells in the bladder itself. The bladder was fibrotic and the luminal side of the bladder epithelium was filled with eosinophilic granules. There was loss of E-cadherin between some epithelial cells, with an enlarged submucosal area filled with immune cells and sometimes invading epithelial cells. We hypothesize that in the absence of AhR there is loss of detoxifying enzymes, which leads to accumulation of unconjugated cytotoxins and carcinogens in the bladder. The presence of bladder toxins may have led to the increased apoptosis and inflammation as well as invasion of epithelial cells in the bladders of older mice.

Original languageEnglish (US)
Pages (from-to)1122-1126
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number4
DOIs
StatePublished - Jan 24 2012

Keywords

  • 2,3,7,8-tetrachlorodibenzoparadioxin
  • Bladder toxicity
  • Gout
  • Uricase
  • Xenobiotic

ASJC Scopus subject areas

  • General

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