| First Author | Hasegawa M | Year | 2011 |
| Journal | Biochem Biophys Res Commun | Volume | 405 |
| Issue | 3 | Pages | 405-10 |
| PubMed ID | 21238430 | Mgi Jnum | J:170638 |
| Mgi Id | MGI:4947003 | Doi | 10.1016/j.bbrc.2011.01.042 |
| Citation | Hasegawa M, et al. (2011) The reconstituted 'humanized liver' in TK-NOG mice is mature and functional. Biochem Biophys Res Commun 405(3):405-10 |
| abstractText | 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. |
