[Development of collagen vascular diseases and production of autoantibodies in HTLV-I env-pX transgenic rats].

Human T lymphocyte virus type I (HTLV- I) is now known to be associated with a number of diverse clinical disorders, not only adult T cell leukemia but also HTLV- I associated myelopathy/tropical spastic paraparesis, HTLV- I -associated arthropathy, HTLV- I uveitis, and probably Sjögren's syndrome, T cell alveolitis, polymyositis, and infective dermatitis. To investigate virus-host interactions and pathogenetic mechanisms in these diverse disorders, inbred rat, which is susceptible to HTLV- I infection and develops HAM/TSP-like disease by HTLV- I infection, was used as a host of HTLV- I gene transfer model. HTLV- I LTR-env-pX-LTR construct was injected to rat ova, and two lines of the transgenic rat (env-pX rat) were established. Both lines of env-pX rats expressed HTLV- I env and pX genes in various tissues, and developed a wide spectrum of collagen vascular diseases, including chronic destructive arthritis similar to rheumatoid arthritis, necrotizing arteritis mimicking polyarteritis nodosa, myositis, myocarditis, and chronic sialoadenitis and dacryoadenitis resembling Sjögren's syndrome in humans. Thrombosis and thymic atrophy were also observed. These rats showed hyper-gamma globulinemia and a number of autoantibodies, including high titered rheumatoid factors, anti-dsDNA antibodies and anti-cardiolipin antibodies were presented in the serum. Results suggest that the HTLV- I env-pX gene may play a pathogenic role in development of collagen vascular diseases associated with autoimmune phenomenon. The env-pX rat appears to be a suitable animal model for elucidating pathogenetic mechanisms implicated in HTLV- I -induced diseases and also in various collagen vascular diseases of unknown etiology in humans.