Experiments for the first time have reproduced a form of human arthritis in genetically altered rats and confirmed a previously established link between a gene involved in regulating the immune system and this form of arthritis, researchers said Thursday.
The achievement means researchers now have a reliable animal model to aid studies of ankylosing spondylitis, Reiter’s syndrome, psoriatic arthritis and related diseases.
The rats carry the human genes for a tissue type found in many patients with these diseases, which are collectively known as spondyloarthropathies.
These forms of arthritis are believed to affect about 200,000 Americans, primarily young adults. Other types of arthritis, such as rheumatoid arthritis and osteoarthritis, are more common.
The advances, reported by researchers at the University of Texas Southwestern Medical Center in Dallas, may eventually lead to better treatments and prevention strategies. Their findings are being published today in the journal Cell.
The Dallas researchers injected a solution containing DNA fragments of the two genes that encode for the tissue type into fertilized one-cell rat eggs. They then performed experiments that confirmed that the genes had been incorporated into the genetic material of the rats and that the rats produced protein molecules encoded by the genes.
Several months after birth, the rats develop symptoms similar to those found in the human arthritic diseases, such as arthritis of the spine and large joints, and inflammation of the bowel, skin and nails.
“We are all very pleased with this remarkable scientific advance,” said Dr. Lawrence E. Shulman, director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, which was one of the sponsors of the research. “The discovery clearly shows that genetic factors participate directly in causing (the diseases).”
Shulman added: “Now they need to find out how these genes act and work to produce the arthritic changes, and what, if any, co-factors are involved in this process.”
The development of an animal model “allows us to examine the development of the disease from its very earliest stages,” said Dr. Joel D. Taurog, one of the researchers.
About 7% or 8% of Americans are believed to carry genes for the tissue type HLA-B27. This tissue type is also present in the vast majority of individuals who develop spondyloarthropathies, an association that was first noted in 1973.
Researchers seeking to understand these diseases have been puzzled by the fact that only a minority of individuals--estimates vary from 1% to 20%--with the HLA-B27 tissue type become ill. One theory is that the diseases are triggered by exposure to certain types of intestinal bacteria. Another is that some individuals with the HLA-B27 tissue type make a protein encoded by the genes, and therefore become ill, while others do not make the protein and remain well.
“The findings provide strong evidence that the B-27 gene is directly involved in causing the disease,” Taurog said.
The University of Texas researchers and others had previously conducted similar experiments in mice, but the animals did not become ill. They now hope to study the effects of various drugs on the development of arthritis in the rats and try to learn more about the changes in the rats which initiate the development of disease.
These are major forms of the group of arthritic diseases known as spondyloarthropathies. An estimated 7% of Americans have a genetic predisposition to developing these diseases, but only a minority of these individuals do so.
ANKYLOSING SPONDYLITIS: This ailment causes pain and stiffness in the joints of the body’s trunk, including the back, neck, hips, shoulders and ribs. In severe cases, a stiff and inflexible spine can develop, as well as eye, heart and other complications.
ARTHRITIS OF INFLAMMATORY BOWEL DISEASE: Some patients with the bowel disorders ulcerative colitis or Crohn’s disease develop arthritis, primarily in the hands and feet.
PSORIATIC ARTHRITIS: Individuals who have the skin disease psoriasis sometimes have an accompanying joint inflammation, especially in the knees and elbows.
REITER’S SYNDROME: A type of arthritis transmitted by sexual contact that is the most common cause of arthritis in young men. Features include pain in the joints, eye inflammation, skin rash and a penile discharge.