The researchers transplanted human liver cells into immunodeficient mice and allowed them to grow in the mice, gradually forming a human-mouse chimeric liver. In this animal model, HBV can survive in human liver cells and be humanized, a mouse hepatitis B animal model.

       [Modeling mechanism] In order to prepare a humanized animal model of hepatitis B, the mouse to establish the humanized model is an immunodeficient mouse. You need to be immune to mutations. Defective mice, such as SCID mice. Because immunodeficient animals show good tolerance to foreign hepatocytes, there is basically no rejection reaction, which is the basic condition for human hepatocyte transplantation. Since human hepatocytes are sensitive to HBV, this humanized mouse can be used for HBV research.

[Modeling method]: irradiate CB6F1 mice with 60Co-γ rays (4Gy, 11Gy after 3 days, 0.7Gy/min) to destroy the immune system and bone marrow, and intravenously inject SCID/OD mouse bone marrow cells (4× 1000000 to 6×1000000) transplanted under the kidney capsule containing exogenous HBV-infected human liver tissue. For BNX mice, a single dose of 11 Gy can be transplanted into human liver tissue 10 days after bone marrow transplantation.

　　 OD/SCID mouse HBV model: Human liver cells (4x1000000) are mixed with Matrigel and transplanted under the mouse kidney capsule. For the first 57 days, 50 μg c-Met antibody was injected intravenously every 2 weeks. The level of α1 antitrypsin is used to assess the proliferation of human hepatocytes. Then inoculate HBV and test HBsA9 and HBV-DNA. Mouse HBV model deficient in recombination activator gene 2 (RAG-2): RAG-2 deficiency can lead to comprehensive immune deficiency in mouse body fluids and cells. First, prepare immortal HBV-carrying IHBV6.7 hepatocytes and inject them into the spleens of RAG-2 deficient mice. Immortalized IHBV6.7 hepatocytes survive in the liver of mice and can secrete HBV. Urokinase-type plasminogen activator (urokinase-type plasminogen activator, uPA) transgenic mouse model: uPA expression is hepatotoxic, and may cause the death of hepatocytes carrying the gene to produce hepatocyte regeneration signals and Human-derived hepatocytes subsequently introduced by plants are beneficial to growth. Using this method, researchers crossed uPA transgenic mice with SCID or RAG-2 deficient mice, and the resulting uPA/SCID or RAG-2 mice were more suitable for the growth of transplanted liver cells. And occupy most of the liver cells. Prepared for humanized liver sensitive to HBV. [Characteristics of the model] Human hepatocytes surviving in the HBV-Trimera mouse model can replicate the HBV replication process after infecting the human liver. About 80% of the mice can detect viremia. OD/SCID mouse HBV model can support HBV infection and replication. Although the virus titer in the blood is not high, they can exist for a long time. The advantage of the AG-2 deficient mouse HBV model is that humanized hepatocytes can survive long-term in the microenvironment of the mouse liver and maintain biological functions. uPA/SCID or RAG-2 mice are ideal mouse models for humanization, which are closer to the actual situation of human liver infection with HBV. [Model evaluation and application] The HBV-Trimera mouse model has been previously developed, but its serum virus titer is low and can only be maintained for about 20 days, which can be used for short-term research of antiviral drugs. There are disadvantages. The OD/SCID mouse HBV model and the RAG-2 deficient mouse HBV model can make human hepatocytes survive longer in mice, and provide an excellent model for comprehensive evaluation of antiviral drugs. However, when preparing an HBV model for RAG-2 deficient mice, it is time-consuming to establish an immortalized hepatocyte line, and the proliferation rate of hepatocytes is not high. uPA/SCID or RAG-2 mice are not only suitable for studying antiviral drugs, but also for studying the molecular mechanism of the interaction between HBV and the host. The disadvantage of humanized mice is that they require fresh human liver cells for construction, which limits their applications to a certain extent. In addition, humanized mice are mainly immunodeficient mice, and it is difficult to study the immune response caused by viruses.