Generation of transplantable and gene therapy model rats using IL2 receptor gamma KO rat derived from rat pluripotent stem cell

2013 Fiscal Year Final Research Report

• Project/Area Number: 23500490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: The University of Tokyo
• Principal Investigator: HAMANAKA SANAE 東京大学, 医科学研究所, 特任研究員 (40511415)
• Project Period (FY): 2011 – 2013
• Keywords: X-SCID / 移植 / ラットES細胞 / ラットiPS細胞 / IL2レセプターγ遺伝子

Research Abstract

We generated a model rat of the X-linked serious case combined immunodeficiency disease (X-SCID) by homologous recombination with IL2 receptor gammma gene using rat pluripotent stem cells. T cells, B cells and natural killer cells and the thymus were decreased in the X-SCID rat and it showed the serious case immune deficiency disorder.
It was suggested that the X-SCID rat was useful as a model of the cell transplantation of a neoplastic cell of human and mouse hematopoietic stem cells, even though the human hematopoietic stem cells were not able to reconstitution.

Research Products

• [Journal Article] Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells (2013)
  • Author(s): Yamamoto R, Morita Y, Ooehara J, Hamanaka S, Onodera M, Rudolph KL, Ema H, Nakauchi H
  • Journal Title: Cell Volume: 154(5) Pages: 1112-26
  • Peer Reviewed
• [Journal Article] Generation of transgenic mouse line expressing Kusabira Orange throughout body, including erythrocytes, by random segregation of provirus method (2013)
  • Author(s): Hamanaka S, Ooehara J, Morita Y, Ema H, Takahashi S, Miyawaki A, Otsu M, Yamaguchi T, Onodera M, Nakauchi H
  • Journal Title: Biochem Biophys Res Commun Volume: 435(4) Pages: 586-91
  • Peer Reviewed
• [Journal Article] Development of an all-in-one inducible lentiviral vector for gene specific analysis of reprogramming (2012)
  • Author(s): Yamaguchi T, Hamanaka S, Kamiya A, Okabe M, Kawarai M, Wakiyama Y, Umino A, Hayama T, Sato H, Lee YS, Kato-Itoh M, Masaki H, Kobayashi T, Yamazaki S, Nakauchi H
  • Journal Title: PLoS One Volume: 7(7) Pages: e41007
  • Peer Reviewed
• [Journal Article] Distinct B-cell lineage commitment distinguishes adult bone marrow hematopoietic stem cells (2012)
  • Author(s): Ghosn EE, Yamamoto R, Hamanaka S, Yang Y, Herzenberg LA, Nakauchi H, Herzenberg LA
  • Journal Title: Proc Natl Acad Sci USA Volume: 109(14) Pages: 5394-8
  • Peer Reviewed
• [Journal Article] Generation of germline-competent rat induced pluripotent stem cells (2011)
  • Author(s): Hamanaka S, Yamaguchi T, Kobayashi T, Kato-Itoh M, Yamazaki S, Sato H, Umino A, Wakiyama Y, Arai M, Sanbo M, Hirabayashi M, Nakauchi H
  • Journal Title: PLoS One Volume: 6(7) Pages: e22008
  • Peer Reviewed
• [Presentation] GENERATION OF GERMLINE COMPITENT RAT INDUCED PLURIPOTENT STEM CELL (2011)
  • Author(s): Sanae Hamanaka
  • Organizer: ISSCR 9th Annual Meeting
  • Place of Presentation: Toronto, Ontario Canada
  • Year and Date: 20110615-18