Humanized Liver Mouse Model for HBV

NOD.Cg-Prkdc^scid Il2rg^tm1Sug Tg(Alb-UL23)7-2/ShiJic (TK-NOG) mice are a specially designed strain (43 (link)) that allows for the conditional depletion of mouse hepatocytes and engraftment of their human cell counterparts. We used these animals as previously described (12 (link)). Eight- to 10-week-old TK-NOG male mice were selected by genotyping and injected with ganciclovir (10 and 30 mg/kg) 7 and 5 days to achieve significant damage of mouse liver as evident by elevated to ALT levels (200 to 400 IU/ml) before transplantation of human hepatocytes. Human hepatocytes were obtained from Lonza (lot no. 4145; Walkersville, MD, USA). Two million hepatocytes were intrasplenically infused. The levels of hepatocyte engraftment were monitored starting from 1 month after transplantation. The chimerism rate correlated with serum hAlb levels (43 (link)) measured using the Human Albumin ELISA Kit (Bethyl Laboratories Inc., Montgomery, TX). At 2 months after transplantation, animals were intravenously infected with patient-derived sera samples containing ~10⁶ HBV DNA, and the drug treatment was started at 2 months after infection. Overall, the mice were followed for 3 months after drug injection. The duration of experimental animal life reached ~9 months.