Featured Research

from universities, journals, and other organizations

Researchers Identify Roles Of Gene Mutations Causing Lupus In Mice

Date:
June 15, 2006
Source:
UT Southwestern Medical Center
Summary:
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.

Dr. Edward Wakeland, professor of immunology and director of the Center for Immunology, directed a research group including center assistant instructor Katalin Tus who discovered 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.
Credit: UT Southwestern Medical Center

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.

Related Articles


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 disease – the mouse dies of the mouse version of SLE," said Dr. Wakeland, who is also a contributing author to the Science paper.

The faulty gene mechanism described by Dr. Wakeland's lab occurs in the body's basic or innate immune system, which recognizes an initial infection and responds to very generic forms of single-stranded viral RNA.

In contrast, Dr. Mohan's group explained a key mechanism in the development of lupus occurring in the adaptive immune system, which consists of cells that constantly adapt themselves to better recognize invading organisms and produce antibodies to fight them.

Both studies could yield promising targets for the development of specific drugs to treat or prevent human lupus, Drs. Mohan and Wakeland said.

Many of the current medications for lupus are drugs that were developed to treat other diseases. Such lupus medications include corticosteroids, chemotherapy drugs and the malaria drug Plaquenil.

"The available treatments are non-specific and can often cause undesirable side effects," Dr. Mohan said.

Lupus is a chronic disease that can cause life-threatening damage to many parts of the body, including the kidneys, lungs, heart, central nervous system, joints, blood vessels and skin. It can be associated with severe fatigue, joint pain, skin rashes, hair loss and neurological problems.

Genetic predisposition, gender and race are major risk factors for lupus, which affects an estimated 270,000 to more than one million people in the United States. Women are five times more likely to die from lupus than men, and African-Americans are three times more like to die from lupus than Caucasians, according to the Alliance for Lupus Research. It is also more common in women of Hispanic, Asian and Native-American descent. Nine out of 10 people with lupus are women.

Other UT Southwestern researchers involved with the Ly108 study in Science are: Dr. Liunan Li, postdoctoral fellow in immunology; Mei Yan, research assistant; Madhavi Bhaskarabhatla, research assistant; Angela Mobley, senior flow cystometry specialist; Charles Nguyen, graduate student in UT Southwestern's Medical Scientist Training Program; Jill Mooney, graduate student in immunology; and Dr. John Schatzle, associate professor of immunology. The study was funded by the National Institutes of Health and the Lupus Research Institute.

Other UT Southwestern authors of the PNAS paper on Tlr7 are: lead author Dr. Srividya Subramanian, a former postgraduate student in the Center for Immunology, now a postdoctoral researcher at Harvard University; Dr. Katalin Tus, assistant instructor, Dr. Quan Li, assistant professor, Xiang-Hong Tian, research scientist, Jinchun Zhou, senior research associate, and Chaoying Liang, senior research associate, all in Center for Immunology; Andrew Wang, graduate student, Medical Scientist Training Program; Guy Bartov, research technician in pathology; Dr. Lisa McDaniel, assistant professor of pathology; Dr. Xin Zhou, associate professor of pathology; and Dr. Roger Schultz, associate professor of pathology. The study was supported by the NIH, the Lupus Research Institute and the Alliance for Lupus Research.


Story Source:

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


Cite This Page:

UT Southwestern Medical Center. "Researchers Identify Roles Of Gene Mutations Causing Lupus In Mice." ScienceDaily. ScienceDaily, 15 June 2006. <www.sciencedaily.com/releases/2006/06/060615181054.htm>.
UT Southwestern Medical Center. (2006, June 15). Researchers Identify Roles Of Gene Mutations Causing Lupus In Mice. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2006/06/060615181054.htm
UT Southwestern Medical Center. "Researchers Identify Roles Of Gene Mutations Causing Lupus In Mice." ScienceDaily. www.sciencedaily.com/releases/2006/06/060615181054.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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