Scripps research scientists find new genetic mutation that halts the developmen... ( The new study was published in the J...)

Scripps research scientists find new genetic mutation that halts the development of lupus

Date:1/17/2008

The new study was published in the January 18 edition (Volume 28, Issue 1) of the journal Immunity.

The lupus-suppressing action is the result of what is known as a nonsense mutation of the Coronin-1A gene (Coro1a) required for the development of the disease. A nonsense mutation causes the gene to produce proteins that no longer function. The Coronin-1A gene is a multifunctional regulator of the cytoskeleton, a network of protein fibers or filaments in the cell that helps maintain cell shape and is the key contributor to cell movement.

The mutation reduced symptoms of the disease by interfering with the development and activation of T cells and other immune responses, said Dwight Kono, an associate professor at The Scripps Research Institute. These findings solidify the critical role of Coronin-1A in normal immune responses, and identify it as a potential therapeutic target for lupus.

Two Sides of Lupus Genetics

Systemic lupus erythematosus is a serious autoimmune disease that affects approximately 1.5 million Americans. It is influenced by genetic, environmental, and hormonal factors, although genetic predisposition appears to be the single greatest contributor to its onset.

There has been considerable interest in defining the genetics of systemic lupus erythematosus in recent years, not only for gaining a better understanding of the fundamental causes of the disease but also for the development of potential therapies.

We were searching for a lupus susceptibility gene, Kono said. After mapping and cloning the Coronin-1A gene, we discovered this spontaneous mutation in a single strain of mice-those that dont get severe or systemic lupus-like disease. More than likely, the mutation had existed undetected in our mouse colony for years.

We ended up cloning a disease-resistance gene when we were thinking about doing the opposite, he continued. Suppressive genes may, in fact, play an important r
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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