As a leading provider of preclinical drug development services, Creative Biolabs is offering an integrated portfolio of rodent disease models. Especially, we provide mouse models of Hepatitis B virus to facilitate the elucidation of the mechanisms underlying chronic HBV infection and the evaluation of new antiviral drugs.

The Introduction of Hepatitis B Virus

Hepatitis B virus (HBV) is a noncytopathic, enveloped virus with a circular, double-stranded DNA genome. The infection of HBV will result in acute or chronic necroinflammatory liver diseases. Moreover, chronic HBV infection is the major cause of hepatic cirrhosis and hepatocellular carcinoma (HCC), leading to high death rates. Although an effective vaccine was introduced years ago, the percentage of existing HBV carriers remains high and vaccination is not a treatment for established infections. As a result, effective animal models of HBV are indispensable for both mechanism studies and the development of novel therapeutic interventions.

The Introduction of HDI Technique

Gene delivery methods are essential for both therapeutic intervention and as research tools to address specific questions. The advent of the hydrodynamic injection (HDI) has greatly facilitated the delivery and expression of genetic material in target cells through an intravenous injection. Currently, HDI represents a valuable technique to induce liver-specific hepatitis B virus (HBV) expression in mice.

The HDI method involves a large bolus injection of your nucleic acid of choice into the tail veins of mice in a volume equivalent to 8% body weight in a time range of 3-5 s. Due to the large hydrodynamic force induced by the injection, the liver fenestrae are expanded, allowing the genetic material to enter into the hepatocytes. Once the delivered genetic material has entered the hepatocytes and the hydrodynamic pressure subsides, the fenestrae close up, trapping the information inside the cells.

AAV/HBV-Induced Chronic HBV Infection Rodent ModelFig.1 De novo anti-HBsAg generation and serum level of alanine aminotransferase (ALT). (Zhu et al. 2016)

Features of Chronic HBV Infection Mouse Models

Creative Biolabs provides a non-transgenic model of persistent HBV infection in immunocompetent mice. Briefly, it can be established via HDI of a replication-competent HBV DNA, pAAV/HBV1.2, into the mice, resulting in expression of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B core antigen (HBcAg), and high levels of serum HBV DNA. The model exhibits advantages such as:

  • Stochastic flares of serum HBV-DNA, resembling the oscillating pattern of viral control in humans with chronic HBV infection.
  • Allowing the interrogation of immune and cell death signaling pathways involved in the host response to HBV.
  • Sharing many similarities with human chronic HBV infections in the immune tolerant stage.

Assessments

After the injection, serum specimens are assayed for the presence of HBV antigen or antibody at the indicated times. Liver tissues can be isolated for immunohistochemical analysis. Creative Biolabs provides various assessments to study the efficacy of potential therapeutics, including but not limited to:

  • Serum HBV DNA detection
  • Serum HBsAg, HBeAg, HBsAb measurement
  • Serum alanine aminotransferase (ALT) measurement
  • Immunohistochemistry

Meanwhile, Creative Biolabs also offers other types of rodent digestive system disease models that you may be interested in. They are listed as follows for you to review:

Additionally, Creative Biolabs offers turn-key or ala carte services customized to our client's needs. Contact us to discuss your specific requirements if you would like to propose a new model or customize an existing model to meet your particular research needs. If you're interested in our services, contact us for more information.

Reference

  1. Zhu, D.; et al. Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy to Reverse Tolerance for an Effective Therapeutic Vaccination[J]. Journal of Immunology. 2016, 196(7):3079.

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