Featured Research

from universities, journals, and other organizations

Jefferson Scientists Create First Transgenic Mouse Model Of Hepatitis B-Based Liver Disease

Date:
July 29, 1999
Source:
Jefferson Medical College
Summary:
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.

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 the development of new approaches against the latter," says Dr. Feitelson, noting that many individuals with acute disease recover.

The mouse model may also have major implications for developing drugs against diseases that remain a major international public health problem. "One of the largest problems in the field of hepatitis B is what to do with carriers at high risk for the development of chronic liver diseases," Dr. Feitelson says. "We have a vaccine to prevent the disease and tests to screen the blood supply, but there are still an estimated 350 million HBV carriers at high risk of developing hepatitis, cirrhosis, and liver cancer." As many as 2 billion people worldwide are infected with the virus, though they are not carriers. Chronic HBV infection is the ninth leading cause of death in the world, accounting for more than 1 million deaths in 1996 alone.

The new model opens up several opportunities for scientists studying HBV. While scientists know that the pathogenesis of chronic hepatitis B is due to immune responses against the virus-infected liver cells, "There are basic science questions of pathogenesis that are unsolved and which can be addressed by this model," Dr. Feitelson says.

The HBV transgenic SCID mouse provides an easily manipulated model for both basic and applied research compared to wild animals, such as woodchucks, ground squirrels and ducks, which are naturally infected with hepatitis B-like viruses.

"We can test drugs in the liver against the virus in the absence of disease – if we don’t reconstitute the immune system," Dr. Feitelson says. "Or we can replace the immune system and then ask what the drug does to the virus and disease."

The model is both powerful and flexible, he says. It will enable scientists to target the liver with viral gene therapy, decide which virus proteins are targets for immunological responses, and identify the parts of the immune system important for targeting the virus.

The model has broad implications for studying the pathogenesis of other selected diseases. "Scientists can use the same approach to study the pathogenesis of immune-mediated diseases against other infectious agents and in selected autoimmune diseases," he explains. "For something that is foreign, you can reconstitute the immune system and look for development of pathology to that foreign protein."

For more information about participating in the clinical trial, please call 1-800-JEFF NOW.


Story Source:

The above story is based on materials provided by Jefferson Medical College. Note: Materials may be edited for content and length.


Cite This Page:

Jefferson Medical College. "Jefferson Scientists Create First Transgenic Mouse Model Of Hepatitis B-Based Liver Disease." ScienceDaily. ScienceDaily, 29 July 1999. <www.sciencedaily.com/releases/1999/07/990729074449.htm>.
Jefferson Medical College. (1999, July 29). Jefferson Scientists Create First Transgenic Mouse Model Of Hepatitis B-Based Liver Disease. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/1999/07/990729074449.htm
Jefferson Medical College. "Jefferson Scientists Create First Transgenic Mouse Model Of Hepatitis B-Based Liver Disease." ScienceDaily. www.sciencedaily.com/releases/1999/07/990729074449.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins