Comparisons among the three human liver chimeric mouse models

Development/genotypeDandri et al. (2001)1 alb-uPA/Rag2−/−Bissig et al. (2007)Hasegawa et al. (2011b)
Mercer et al. (2001)2 – alb-uPA/SCID/BgAzuma. et al. (2007)Alb-HSVtk/SCID/Il2rg−/−
Tesfaye et al. (2013)3 – mup-uPA/SCID/BgFRG
Tateno et al. (2015)4 – alb-cDNA-uPA/SCID
Mechanism of murine liver injuryIntoxication by liver overexpression of uPA 1–4Accumulation of toxic tyrosine catabolitesGeneration of a toxic ganciclovir metabolite by expression of HSVtk in the liver
AdvantagesMost experienceInducible systemInducible system
Hepatocyte transplantation at any ageHepatocyte transplantation at any age
DrawbacksNoninducible murine liver injury due to a constitutive uPA expression 1–4Human hepatocyte repopulation requires small molecular drug (nitisinone)Repopulation efficiency more hepatocyte donor dependent than other models
Narrow window of hepatocyte transplantation 1,2,4Kidney disease due to FAH deficiencySelection pressure only applied before hepatocyte transplantation
High postnatal mortality due to internal bleeding 1,2,4Cancer model with frequent liver tumorsLow 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