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Biochem Biophys Res Commun. 2011 Feb 18;405(3):405-10. doi: 10.1016/j.bbrc.2011.01.042. Epub 2011 Jan 14.

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

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  • 1Biomedical Research Department, Central Institute for Experimental Animals, 1430 Nogawa, Miyamae, Kawasaki, Kanagawa 216-0001, Japan.

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21238430
[PubMed - indexed for MEDLINE]
PMCID:
PMC3648850
Free PMC Article
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