Selective depletion of mouse kidney proximal straight tubule cells causes acute kidney injury

Michiko Sekine, Toshiaki Monkawa, Ryuji Morizane, Kunie Matsuoka, Choji Taya, Yoshiko Akita, Kensuke Joh, Hiroshi Itoh, Matsuhiko Hayashi, Yoshiaki Kikkawa, Kenji Kohno, Akemi Suzuki, Hiromichi Yonekawa

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The proximal straight tubule (S3 segment) of the kidney is highly susceptible to ischemia and toxic insults but has a remarkable capacity to repair its structure and function. In response to such injuries, complex processes take place to regenerate the epithelial cells of the S3 segment; however, the precise molecular mechanisms of this regeneration are still being investigated. By applying the "toxin receptor mediated cell knockout" method under the control of the S3 segment-specific promoter/enhancer, Gsl5, which drives core 2 β-1,6-N-acetylglucosaminyltransferase gene expression, we established a transgenic mouse line expressing the human diphtheria toxin (DT) receptor only in the S3 segment. The administration of DT to these transgenic mice caused the selective ablation of S3 segment cells in a dose-dependent manner, and transgenic mice exhibited polyuria containing serum albumin and subsequently developed oliguria. An increase in the concentration of blood urea nitrogen was also observed, and the peak BUN levels occurred 3-7 days after DT administration. Histological analysis revealed that the most severe injury occurred in the S3 segments of the proximal tubule, in which tubular cells were exfoliated into the tubular lumen. In addition, aquaporin 7, which is localized exclusively to the S3 segment, was diminished. These results indicate that this transgenic mouse can suffer acute kidney injury (AKI) caused by S3 segment-specific damage after DT administration. This transgenic line offers an excellent model to uncover the mechanisms of AKI and its rapid recovery.

Original languageEnglish
Pages (from-to)51-62
Number of pages12
JournalTransgenic research
Volume21
Issue number1
DOIs
Publication statusPublished - 2012 Feb 1

    Fingerprint

Keywords

  • Acute kidney injury (acute renal failure)
  • Diphtheria toxin receptor
  • Kidney proximal straight tubules
  • Transgenic mouse

ASJC Scopus subject areas

  • Biotechnology
  • Animal Science and Zoology
  • Agronomy and Crop Science
  • Genetics

Cite this

Sekine, M., Monkawa, T., Morizane, R., Matsuoka, K., Taya, C., Akita, Y., Joh, K., Itoh, H., Hayashi, M., Kikkawa, Y., Kohno, K., Suzuki, A., & Yonekawa, H. (2012). Selective depletion of mouse kidney proximal straight tubule cells causes acute kidney injury. Transgenic research, 21(1), 51-62. https://doi.org/10.1007/s11248-011-9504-z