The reconstituted 'humanized liver' in TK-NOG mice is mature and functional

Masami Hasegawa, Kenji Kawai, Tetsuya Mitsui, Kenji Taniguchi, Makoto Monnai, Masatoshi Wakui, Mamoru Ito, Makoto Suematsu, Gary Peltz, Masato Nakamura, Hiroshi Suemizu

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170 Citations (Scopus)

Abstract

To overcome the limitations of existing models, we developed a novel experimental in vivo platform for replacing mouse liver with functioning human liver tissue. To do this, a herpes simplex virus type 1 thymidine kinase (HSVtk) transgene was expressed within the liver of highly immunodeficient NOG mice (TK-NOG). Mouse liver cells expressing this transgene were ablated after a brief exposure to a non-toxic dose of ganciclovir (GCV), and transplanted human liver cells are stably maintained within the liver (humanized TK-NOG) without exogenous drug. The reconstituted liver was shown to be a mature and functioning " human organ" that had zonal position-specific enzyme expression and a global gene expression pattern representative of mature human liver; and could generate a human-specific profile of drug metabolism. The 'humanized liver' could be stably maintained in these mice with a high level of synthetic function for a prolonged period (8. months). This novel in vivo system provides an optimized platform for studying human liver physiology, including drug metabolism, toxicology, or liver regeneration.

Original languageEnglish
Pages (from-to)405-410
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume405
Issue number3
DOIs
Publication statusPublished - 2011 Feb 18

Keywords

  • Drug metabolism
  • Herpes simplex virus type 1 thymidine kinase (HSVtk)
  • Humanized mouse
  • Liver reconstitution

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Hasegawa, M., Kawai, K., Mitsui, T., Taniguchi, K., Monnai, M., Wakui, M., Ito, M., Suematsu, M., Peltz, G., Nakamura, M., & Suemizu, H. (2011). The reconstituted 'humanized liver' in TK-NOG mice is mature and functional. Biochemical and Biophysical Research Communications, 405(3), 405-410. https://doi.org/10.1016/j.bbrc.2011.01.042