Linked to diabetes? A mouse model suggests that the same genes pose a risk of diabetes and rheumatoid arthritis, which produces swollen joints (above).

Diabetes, Rheumatoid Arthritis Linked by Mouse Model

SAN FRANCISCO--A new model of rheumatoid arthritis in mice supports the theory that many different autoimmune diseases share genetic risk factors, according to research presented on 17 February here at the annual meeting of the American Association for the Advancement of Science, which publishes ScienceNOW. While studying a strain of mice that usually develops diabetes, researchers found that the mice that don't get diabetes develop rheumatoid arthritis instead.

The "common gene" hypothesis for autoimmune diseases has intrigued immunologists for 20 years. They've found some commonalities among such disparate diseases as systemic lupus erythematosus, which attacks skin, kidneys, heart, and brain; scleroderma, which hardens and destroys skin and connective tissue; rheumatoid arthritis, which damages joints; and type I diabetes, which kills insulin-secreting cells in the pancreas. In each case, the body's own (misdirected) immune system causes the damage. Although autoimmune diseases run in families, often only one of a pair of identical twins will get sick; researchers are still trying to puzzle out the overlapping roles of environment and genes.

Hoping to determine what causes genetically similar animals to get an autoimmune disease or not, researchers led by immunologist Denise Faustman of Harvard Medical School in Boston focused on mice that usually develop a disease much like type I diabetes. In each generation, some of the animals get sick and some remain healthy. The researchers bred the healthy mice and raised them to adulthood, in search of a strain with diabetes-linked genes but no disease. To their surprise, they found that 80% of the animals developed symptoms similar to those seen in human rheumatoid arthritis. As in humans with rheumatoid arthritis, the inflammation centered on wrist and large knuckle joints, was more common in female mice, and went into remission during pregnancy.

The researchers hope that comparing the two strains of mice will shed light on how a common genetic defect can develop into a wide array of illnesses. "One of the curiosities of autoimmune diseases is that the same factors that exacerbate one kind of autoimmune disease actually ameliorate others," says Noel Rose, an immunologist at Johns Hopkins University School of Hygiene and Public Health in Baltimore. He says Faustman's work has "shown that there's enough wobble in the translation" between genes and disease to explain that puzzle.

Related sites

American Autoimmune Related Diseases Association

Noel Rose's home page