Urological Research

, Volume 35, Issue 2, pp 89–99 | Cite as

Successful formation of calcium oxalate crystal deposition in mouse kidney by intraabdominal glyoxylate injection

  • Atsushi Okada
  • Shintaro Nomura
  • Yuji Higashibata
  • Masahito Hirose
  • Bing Gao
  • Mugi Yoshimura
  • Yasunori Itoh
  • Takahiro Yasui
  • Keiichi Tozawa
  • Kenjiro Kohri
Original Paper
First Online:
Received:
Accepted:

Abstract

The establishment of an experimental animal model would be useful to study the mechanism of kidney stone formation. A calcium kidney stone model in rats induced by ethylene glycol has been used for research; however, to investigate the genetic basis affecting kidney stone formation, which will contribute to preventive medicine, the establishment of a kidney stone model in mice is essential. This study indicates the optimum conditions for inducing calcium oxalate stones in normal mouse kidney. Various doses of oxalate precursors, ethylene glycol, glycolate and glyoxylate, were administered either by free drinking or intraabdominal injection for 2 months as a preliminary study. Stone formation was detected with light microscopy, polarized light optical microscopy and electron microscopy. Stone components were detected with X-ray diffraction analysis. The expression of osteopontin (OPN), a major stone-related protein, was detected with immunohistochemical staining, in situ hybridization and quantitative reverse transcriptase polymerase chain reaction. Kidney stones were not detected in ethylene glycol- or glycolate-treated groups even at the highest dose of LD50. Whereas, numerous kidney stones were detected in glyoxylate-treated mice (more than 60 mg/kg) at 3, 6 and 9 days after glyoxylate were administered intraabdominally. However, the number of kidney stones decreased gradually at day 12, and was hardly detected at day 15. The stone component was further analyzed as calcium oxalate monohydrate. A dramatic increase in the expression of OPN was observed by the administration of glyoxylate. We established a mouse kidney stone experimental system in this study. The difficulty of inducing kidney stones suggested that mice have greater intrinsic ability to prevent stone formation with hyperoxaluric stress than rats. The differing response to hyperoxaluric stress between mice and rats possibly contributes to the molecular mechanism of kidney stone formation and will aid preventive medicine in the future.

Keywords

Osteopontin Kidney stone Model mouse Calcium oxalate Glyoxylate 
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Notes

Acknowledgments

We would like to thank Ms. A. Makie, Ms. N. Kasuga, Ms. A. Hayashi and Ms. Y. Kobayashi for their expert management of mice and secretarial assistance. This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Science and Technology (No. 12307034, No. 13770889, No. 16790922) and the Aichi Kidney Foundation, Japan.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Atsushi Okada
    • 1
  • Shintaro Nomura
    • 2
  • Yuji Higashibata
    • 1
  • Masahito Hirose
    • 1
  • Bing Gao
    • 1
  • Mugi Yoshimura
    • 1
  • Yasunori Itoh
    • 1
  • Takahiro Yasui
    • 1
  • Keiichi Tozawa
    • 1
  • Kenjiro Kohri
    • 1
  1. 1.Department of Nephro-urologyNagoya City University Graduate School of Medical SciencesNagoya CityJapan
  2. 2.Department of PathologyOsaka University Graduate school of MedicineSuita CityJapan

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