TRANSGENIC MICE EXPRESSING A TRUNCATED PEROMYSCUS-LEUCOPUS TNF-ALPHA GENE MANIFEST AN ARTHRITIS RESEMBLING ANKYLOSING-SPONDYLITIS

Several studies have implicated tumor necrosis factor-alpha (TNF-alpha ) in autoimmune diseases, such as rheumatoid arthritis (RA), To elucid ate further the role of TNF-alpha in inflammatory arthritis, we genera ted transgenic mice harboring a truncated Peromyscus leucopus TNF-alph a (Pe-TNF) gene. An arthritic phenotype closely resembling human ankyl osing spondylitis was observed only in transgenic lines expressing the Pe-TNF transgene at the mRNA level. We characterized the arthritic ph enotype in detail by radiographic and histologic techniques. It consis ted of severe axial skeletal kyphosis and ankylosis, accompanied by an inflammatory and fibrotic process at the end plates and enthesis, Per ipheral joint lesions were absent in mice expressing the P, leucopus T NF-alpha gene, in contrast to the RA-like phenotype described in trans genic mice expressing a truncated human TNF-alpha gene. The Pe-TNF tra nsgenic mouse model provides a unique opportunity to explore potential mechanisms whereby TNF-alpha may initiate an autoimmune arthritis res embling ankylosing spondylitis.