Gene-altered mouse is model for rare autoimmun...( as bacteria and viruses while B cells ...)

While other genetically altered mouse models had been produced that showed similar symptoms, those animals showed other pathologies that do not mimic Sjgren'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 Sjgren'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 Sjgren'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 comple
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Contact: Dennis Meredith
Dennis.mererdith@duke.edu
919-681-8054
Duke University Medical Center
19-Oct-2004