Comparisons among the three human liver chimeric mouse models
| Strain | uPA | FRG | TK-NOG |
|---|---|---|---|
| Development/genotype | Dandri et al. (2001)1 – alb-uPA/Rag2−/− | Bissig et al. (2007) | Hasegawa et al. (2011b) |
| Mercer et al. (2001)2 – alb-uPA/SCID/Bg | Azuma. et al. (2007) | Alb-HSVtk/SCID/Il2rg−/− | |
| Tesfaye et al. (2013)3 – mup-uPA/SCID/Bg | FRG | ||
| Tateno et al. (2015)4 – alb-cDNA-uPA/SCID | |||
| Mechanism of murine liver injury | Intoxication by liver overexpression of uPA 1–4 | Accumulation of toxic tyrosine catabolites | Generation of a toxic ganciclovir metabolite by expression of HSVtk in the liver |
| Advantages | Most experience | Inducible system | Inducible system |
| Hepatocyte transplantation at any age | Hepatocyte transplantation at any age | ||
| Drawbacks | Noninducible murine liver injury due to a constitutive uPA expression 1–4 | Human hepatocyte repopulation requires small molecular drug (nitisinone) | Repopulation efficiency more hepatocyte donor dependent than other models |
| Narrow window of hepatocyte transplantation 1,2,4 | Kidney disease due to FAH deficiency | Selection pressure only applied before hepatocyte transplantation | |
| High postnatal mortality due to internal bleeding 1,2,4 | Cancer model with frequent liver tumors | Low breeding efficiency due to male sterility | |
| Spontaneous deletion of the uPA transgene decreases human hepatocyte repopulation and increases liver tumors incidence 1,2 | |||
| Kidney disorders 1,2 | |||
| Small body size 1,2 | |||
| Female reproductive disorders 1,2 | |||
| High human hepatocyte repopulation requires inhibition of host innate immune response and/or the human complement 1,2 |