To provide a global analysis of genes involved in the inflammatory process in joints of DBA/1J mice suffering from collagen induced arthritis (CIA) we used oligonucleotide microarrays representing approximately 11,000 genes to determine the gene expression profile of the inflamed paws at peak of disease, and compared them to normal tissue. Peak of disease was determined from clinical evaluation of disease and histopathology of joints. Of the 11,000 genes assayed, 223 showed differential expression of four fold or more (187 upregulated and 36 downregulated). Ninety-five of the genes observed had well-characterized full length sequences in databases, and 128 were unknown (Ests). Inflammation resulted in a profile of increased gene expression of matrix metalloproteinases, immune-related, extra-cellular matrix and cell adhesion molecules, as well as molecules involved in cell division and transcription; differential regulation of molecules involved in signal transduction, protein synthesis and metabolism. Of the 55 genes with known chromosomal locations nine mapped to previously identified QTL, contributing to susceptibility or severity of CIA, i.e. MHC class I, II, Basigin, FAP, Cathepsin K, CD 53, RAF1, glucagon, and retinal taurine transporter. The profile of gene expression supports current theoretical models of disease progression and might open new perspectives for both diagnosis and treatment of arthritis.
Copyright 2002 Elsevier Science Ltd.