IDENTIFICATION OF GENES DOWN-REGULATED IN THE THYMUS BY CYCLOSPORINE-A - PRELIMINARY CHARACTERIZATION OF CLONE CSA-19

Using a novel subtractive hybridization approach, we have identified a set of cDNA clones whose expression is downregulated in the thymus by cyclosporin-A (CsA). A number of regulated genes were identified, but the major focus of this report is the clone termed CsA-19. In the adu lt mouse, CsA-19 is expressed at high levels in lymphoid organs, parti cularly in secondary lymphoid organs such as lymph node and spleen. Cs A-19 expression was also found to be regulated in the brain and liver during mouse development. The full length sequences of the murine and human CsA-19 cDNAs have been determined. Both are 700 nucleotides in l ength and encode a predicted product of 217 amino acids. Comparison of the full length cDNA sequences of murine and human CsA-19 reveal that they are greater than 91% conserved. At the predicted amino acid leve l the homology is even greater, with only two amino acid differences i n 217 residues (99% identity). The high degree of homology between mur ine and human CsA-19 indicates that has there been strong evolutionary pressure to conserve the amino acid sequence of CsA-19, and suggests that CsA-19 may play a critical role both during embryogenesis and in mature lymphoid cells.