Featured Research

from universities, journals, and other organizations

Gene-altered Mouse Is Model For Rare Autoimmune Syndrome

Date:
October 21, 2004
Source:
Duke University Medical Center
Summary:
By knocking out a single gene in mice, immunologists at Duke University Medical Center have mimicked a little-understood autoimmune disorder in humans. In the puzzling disorder, called Sjögren's syndrome, the person's tear and salivary glands are affected, causing dry eyes and mouth, as they are damaged by an attack of the person's own immune cells.

DURHAM, N.C. -- By knocking out a single gene in mice, immunologists at Duke University Medical Center have mimicked a little-understood autoimmune disorder in humans. In the puzzling disorder, called Sjögren's syndrome, the person's tear and salivary glands are affected, causing dry eyes and mouth, as they are damaged by an attack of the person's own immune cells.

According to researchers, the achievement not only offers insight into Sjögren's syndrome, but into the general developmental machinery of the immune system.

The immunologists, Yuan Zhuang, HongMei Li and MeiFang Dai, published their findings in the October 2004 issue of the journal Immunity. The work was sponsored by the National Institutes of Health and the Leukemia and Lymphoma Society.

In a preview of the article, immunologist Marjan Versnel wrote that the new mouse model "offers a wonderful opportunity to study in detail the relationship between the immune system and autoimmunity occurring in the context of only a single genetic lesion." Versnel is at Erasmus Medical Center in the Netherlands.

According to Zhuang, while Sjögren's syndrome is not well known, affecting up to 0.6 percent of the population. It manifests itself in middle age, mostly in women.

"Most patients do not see a physician unless it becomes very serious or other problems arise, such as fatigue, arthritis, or inflammation of the lungs, kidneys or blood vessels," he said. Treatment for the disorder involves lubricant drops for the eyes and drugs that increase production of saliva.

"Basically nothing was known about the genetic basis of the disease," said Zhuang. "It was only known that the patients showed infiltration of lymphocytes into lachrymal and salivary glands and the production of certain autoantibodies." Lymphocytes are white blood cells -- T cells and B cells -- that are major components of the immune system. T cells are those that directly attack invaders such as bacteria and viruses, while B cells are the armament factories of the immune system, producing antibodies that recognize and attack such invaders.

While other genetically altered mouse models had been produced that showed similar symptoms, those animals showed other pathologies that do not mimic Sjögren's syndrome, said Zhuang. Also, they did not arise from a single genetic mutation, so it is difficult to determine the initial cause of the disease in these complex animal models, he said.

Zhuang and his colleagues did not set out to produce a mimic of Sjögren's syndrome in their studies. Rather they were exploring the role of a regulatory protein, called Id3, that previous studies in Zhuang's laboratory had revealed to be key to the development of lymphocytes.

"In our basic studies, we suspected that if we developed animal models lacking the gene we would not only better understand its role in immune development, but see disease characteristics as well," said Zhuang. "We had no prior knowledge that we would produce such a precise model of Sjögren's syndrome."

Indeed, he said, the mice lacking the gene had all the characteristics of the disease, including reduced tear and saliva secretion and infiltration of lymphocytes into their tear and salivary glands. The animals also showed production of the antibodies that indicated the immune system was activated to attack the animals' own tissues.

Also, the researchers found that they could induce symptoms of the syndrome in normal mice by transferring bone marrow cells from the genetically altered mice. Bone marrow is the source of immune cells that could cause the disorder. The researchers' experiments with the Id3-deficient mice also revealed that T cells play a dominant and essential role in generating the pathology of the disorder.

According to Zhuang, development of the model will now enable the researchers to explore the complexities of the disease and the immune system in general.

"This model really tells us that the biology of Id3 and the immune system is more complex than was suspected," he said. "For example, we need to understand why autoimmunity so specifically affects the lachrymal and salivary glands when the Id3 gene is very broadly expressed in many cell types."

Thus, the researchers are exploring the mechanism by which the Id3 mutation compromises early development of T cells and produces an autoimmune response.

Importantly, said Zhuang, genetic analysis can be further applied to this animal model. For example, the defect in Id3 may cause different effects in different strains of mice with other genetic deficiencies -- offering even further opportunity for understanding the intricacies of immune system development.

Zhuang and his colleagues are also collaborating with medical center rheumatologists Drs. William St. Clair and Rob Geletka to determine whether Id3 deficiency plays a role in the disease in humans. They have begun to screen blood samples from patients with the disorder.


Story Source:

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


Cite This Page:

Duke University Medical Center. "Gene-altered Mouse Is Model For Rare Autoimmune Syndrome." ScienceDaily. ScienceDaily, 21 October 2004. <www.sciencedaily.com/releases/2004/10/041020093934.htm>.
Duke University Medical Center. (2004, October 21). Gene-altered Mouse Is Model For Rare Autoimmune Syndrome. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2004/10/041020093934.htm
Duke University Medical Center. "Gene-altered Mouse Is Model For Rare Autoimmune Syndrome." ScienceDaily. www.sciencedaily.com/releases/2004/10/041020093934.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) — Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) — Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) — A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) — The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
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