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Jefferson scientists create first transgenic mouse model of hepatitis B-based liver disease

The work holds promise for understanding the mechanisms of disease and for drug discovery

Researchers at Jefferson Medical College have developed the first mouse model of chronic liver disease caused by hepatitis B virus (HBV), which promises to accelerate the discovery of drugs against the disease. Such a model may provide a better understanding of how HBV actually causes liver disease.

Mark A. Feitelson, Ph.D., professor of pathology, anatomy and cell biology at Thomas Jefferson University in Philadelphia and his colleagues there developed transgenic mice that are chronic carriers of HBV. These mice were made by introducing the HBV genetic information into mouse eggs, and breeding mice that had viral DNA in all of their cells. Such mice consistently replicate HBV, which is detected in their blood, throughout their lives. Although other similar models have been made using normal mice, none develop chronic liver disease because the immune system sees the virus as -- self -- during embryonic development.

To solve this problem, Dr. Feitelson used severe combined immunodeficient (SCID) mice as viral hosts. These SCID mice lack critical immune system elements that normally would fight the virus. When the mice are reconstituted with a normal immune system in a procedure akin to bone marrow transplantation, they do not recognize the virus as -- self-- and develop liver disease.

The researchers report their results in August in the journal Nature Medicine.

"The mice see the virus as foreign, which is what they should do," Dr. Feitelson explains. This is similar to the way the human immune system recognizes HBV shortly after exposure to the virus, he points out.

In addition to chronic liver disease, these mice have also been manipulated to develop acute disease. "The differences between acute and chronic disease in these mice will be key to th
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Contact: Steve Benowitz
steven.benowitz@mail.tju.edu
215-955-6300
Thomas Jefferson University
28-Jul-1999


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