For the first time, a form of human arthritis has been reproduced in genetically altered rats, clearing the way for a better understanding of the cause of a family of arthritic diseases that disables 200,000 Americans, primarily young adults.
The work of two Texas investigators was hailed today as a "remarkable scientific advance" by Dr. Lawrence E. Shulman, a rheumatologist and the director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
The achievement holds promise for helping specialists to better diagnose and treat arthritic disorders of spinal and other joints that are grouped under a tongue-twisting name -- spondyloarthropathies.
These disorders can cause painful inflammation of the spine, peripheral joints, eye, bowel, and genital and urinary tracts. In one of the diseases, ankylosing spondylitis, the joints of the spine actually stiffen and fuse. Other types of arthritis, such as rheumatoid arthritis and osteoarthritis, are more common.
The findings of Dr. Joel D. Taurog, a University of Texas Southwestern Medical Center rheumatologist, and Dr. Robert E. Hammer, a Howard Hughes Medical Institute cell biologist in Dallas, were published today in the journal Cell.
"The discovery clearly shows that genetic factors participate directly in causing the diseases," said Shulman. "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 the process."
Taurog and Hammer said their experiments with the genetically altered rats confirm a previously reported link between a gene involved in regulating the immune system and this group of arthritic disorders.
The researchers for the first time have been able to produce two strains of rats that carry the human genes for the genetic marker HLA-B27, which is found in a large percentage of patients with spondyloarthropathies.
More than 90 percent of patients with ankylosing spondylitis have been found to have this marker. In comparison, only 8 percent of the general population carries it.
Beginning about two to three months after birth, the genetically altered rats spontaneously develop all the symptoms of spondyloarthropathies.
The arthritic disorder that occurs in the animal model developed by Taurog and Hammer "strikingly mimics" virtually all of the manifestations of these distressing and disabling diseases of young people, mostly men," the researchers said.
The spondyloarthropathies are classified as rheumatic disorders because the most common complaints associated with them are joint inflammation and pain. However, all can involve more than one organ system, particularly the gastrointestinal and the genitourinary tracts, as well as the skin, eyes and heart.
Once a common genetic marker was identified for these diseases in 1973, it was speculated that a common mechanism might underlie the association with the B27 gene, the researchers said.
Until now, efforts to piece together the various clues have been hampered by the lack of a suitable animal model.