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

Research output: Contribution to journalArticlepeer-review

256 Citations (Scopus)


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
Issue number3
Publication statusPublished - 2011 Feb 18


  • 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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