There on Poster 8 is the family that they studied; the affected members of the family are shown in black. Some of them are young people. These investigators contacted researchers at a center for molecular medicine in Philadelphia, who used the techniques of molecular biology to discover the specific genetic defect. In all nine members in this family who had the osteoarthritis, and in none of the 10 members of the family who didn't have the arthritis, they found this specific defect. It was not found in any of the 57 controls. Collagen-II is a very long protein. It consists of over a thousand amino in three chains, spun around in a spiral. The defect causing the arthritis was found in only one of these one thousand amino acids. It was a substitution of one amino acid for another that caused the defect. This whole area is being pursued. How does this genetic defect cause this arthritis? It provides an exciting new direction for research on this very common form of arthritis. The second discovery, and could we put Poster 9 up now, is just as exciting. This was announced on November 30th. It was made possible by a new biotechnology that produces transgenic animals. The discovery is the successful induction into inbred rats of the human gene for specific forms of spinal arthritis. The human gene is called HLA-B27. As I have listed on Poster 9, not only were they able to introduce the human gene HLA-B27 and create a whole new strain of rats with this human gene, but as they followed the animals, the whole clinical spectrum of the disease appeared without their doing any. thing else, except injecting the gene into these rats. This group of diseases is the most common form of arthritis in young people, affecting men more than women. Ankylosing spondy litis means a disease of spinal arthritis that causes the joints of the spine to become inflamed and fused. You have seen young men with poker spines; that is the type of disease it produces. Reiter's Syndrome gives you a spinal arthritis, and arthritis in big joints, such as wrists and ankles, as well as changes in the nails, and the skin, and inflammation in the genital urinary tract. This is a common form of arthritis in young men. There is also spinal arthritis associated with psoriasis, and spinal arthritis associated with inflammatory bowel disease, and there is reactive arthritis. In 1973, there was a remarkable discovery, made in Los Angeles and in London simultaneously, finding a specific tissue type, HLAB27, in 95 percent of people with ankylosing spondylitis, compared with only 7 percent in the general population. For 17 years, this HLA-B27 genetic marker has remained a mystery as to what this association means. Dr. Taurog, a scientist supported by NIAMS at the University of Texas in Dallas and working in a special arthritis center, joined forces with Dr. Robert Hammer, a Howard Hughes investigator in Dallas, who is an expert on this new transgenic technique, originally developed in Philadelphia. They joined forces and Dr. Hammer took the human gene for a B27, and inoculated it into the fertilized eggs of a strain of rats. They thereby created a new inbred strain and were able to demonstrate that all rats of this new strain carried this human B27 gene. They then observed these rats for a few weeks, and they saw the rats develop spinal arthritis; arthritis in their large joints; they also developed scaling skin changes, and even some nail changes as shown on Poster 10. |