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UT Southwestern researchers identify roles of gene mutations causing lupus in mice

DALLAS In two related studies, researchers at UT Southwestern Medical Center have pinpointed defective genes in mice responsible for triggering the mysterious autoimmune disease lupus, which prompts the body's immune system to mistakenly attack healthy organs and tissues.

A research team led by Dr. Chandra Mohan, associate professor of internal medicine, found that a defect in the Ly108 gene causes immune cells called B-cells to attack the body's healthy cells, resulting in systemic lupus erythematosus, or SLE. Their findings are published in today's issue of the journal Science.

Further research based on the study's findings may lead to better diagnostic tests and therapeutic drugs to help cure human lupus, said Dr. Mohan, the paper's senior author.

"If we can demonstrate that the same gene defect we described in the mouse model also causes human lupus, it would open ways to block the disease by developing therapeutics targeting pathways activated by the mutated Ly108 gene," Dr. Mohan said.

Kirthi Raman Kumar, the paper's lead author and a graduate student in immunology, said, "This is the first demonstration of how immature B-cells from lupus-prone mice behave differently from lupus-resistant normal mice and how this difference can lead to autoimmunity."

In a separate lupus study published online this week in the Proceedings of the National Academy of Sciences, another team of UT Southwestern researchers describe the role of a mutated gene called Tlr7, which interacts with Ly108 in triggering the mechanisms leading to a deadly form of lupus in mice by causing another component of the immune system to malfunction.

The research team led by Dr. Edward Wakeland, professor of immunology and director of UT Southwestern's Center for Immunology, explained that mice that died of lupus carried twice the normal amount of copies of the mutated receptor gene Tlr7.

"If you put both genes together, you create fatal dise
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Contact: Toni Heinzl
Toni.heinzl@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
15-Jun-2006


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