論文

査読有り
2013年7月

Generation of mouse models for type 1 diabetes by selective depletion of pancreatic beta cells using toxin receptor-mediated cell knockout

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Kunie Matsuoka
  • ,
  • Michiko Saito
  • ,
  • Kosuke Shibata
  • ,
  • Michiko Sekine
  • ,
  • Hiroshi Shitara
  • ,
  • Choji Taya
  • ,
  • Xiaohong Zhang
  • ,
  • Tsuneo A. Takahashi
  • ,
  • Kenji Kohno
  • ,
  • Yoshiaki Kikkawa
  • ,
  • Hiromichi Yonekawa

436
3
開始ページ
400
終了ページ
405
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2013.05.114
出版者・発行元
ACADEMIC PRESS INC ELSEVIER SCIENCE

By using the toxin receptor-mediated cell knockout (TRECK) method, we have generated two transgenic (Tg) murine lines that model type I (insulin-dependent) diabetes. The first strain, C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg, carries the diphtheria toxin receptor (hDTR) driven by the human insulin gene promoter, while the other strain, C57BL/6-ins2(BAC)-TRECK-Tg, expresses hDTR cDNA under the control of the mouse insulin II gene promoter. With regard to the C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg strain, only one of three Tg strains exhibited proper expression of hDTR in pancreatic 13 cells. By contrast, hDTR was expressed in the pancreatic beta cells of all four of the generated C57BL/6-ins2(BAC)-TRECK-Tg strains. Hyperglycemia, severe ablation of pancreatic beta cells and depletion of serum insulin were observed within 3 days after the administration of diphtheria toxin (DT) in these Tg mice. Subcutaneous injection of a suitable dosage of insulin was sufficient for recovery from hyperglycemia in all of the examined strains. Using the C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg model, we tried to perform regenerative therapeutic approaches: allogeneic transplantation of pancreatic islet cells from C57BL/6 and xenogeneic transplantation of CD34(+) human umbilical cord blood cells. Both approaches successfully rescued C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg mice from hyperglycemia caused by DT administration. The high specificity with which DT causes depletion in pancreatic beta cells of these Tg mice is highly useful for diabetogenic research. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Web of Science ® 被引用回数 : 4

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2013.05.114
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000321995900009&DestApp=WOS_CPL

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