Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene-altered mouse is model for rare autoimmune syndrome

20.10.2004


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.

Dennis Meredith | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>