Transgenic Mice Expressing a Truncated Peromyscus leucopus TNF-α Gene Manifest an Arthritis Resembling Ankylosing Spondylitis

Abstract

Several studies have implicated tumor necrosis factor-α (TNF-α) in autoimmune diseases, such as rheumatoid arthritis (RA). To elucidate further the role of TNF-α in inflammatory arthritis, we generated transgenic mice harboring a truncated Peromyscus leucopus TNF-α (Pe-TNF) gene. An arthritic phenotype closely resembling human ankylosing spondylitis was observed only in transgenic lines expressing the Pe-TNF transgene at the mRNA level. We characterized the arthritic phenotype in detail by radiographic and histologic techniques. It consisted of severe axial skeletal kyphosis and ankylosis, accompanied by an inflammatory and fibrotic process at the end plates and enthesis. Peripheral joint lesions were absent in mice expressing the P. leucopus TNF-α gene, in contrast to the RA-like phenotype described in transgenic mice expressing a truncated human TNF-α gene. The Pe-TNF transgenic mouse model provides a unique opportunity to explore potential mechanisms whereby TNF-α may initiate an autoimmune arthritis resembling ankylosing spondylitis.