STRUCTURAL CHARACTERIZATION AND CHROMOSOMAL LOCATION OF THE MOUSE MACROPHAGE-MIGRATION INHIBITORY FACTOR GENE AND PSEUDOGENES

Macrophage migration inhibitory factor, MIF, is a cytokine released by T-lymphocytes, macrophages, and the pituitary gland that serves to in tegrate peripheral and central inflammatory responses. Ubiquitous expr ession and developmental regulation suggest that MIF may have addition al roles outside of the immune system. Here we report the structure an d chromosomal location of the mouse Mif gene and the partial character ization of five Mif pseudogenes. The mouse Mif gene spans less than 0. 7 kb of chromosomal DNA and is composed of three exons. A comparison b etween the mouse and the human genes shows a similar gene structure an d common regulatory elements in both promoter regions. The mouse Mif g ene maps to the middle region of chromosome 10, between Ber and S100b, which have been mapped to human chromosomes 22q11 and 21q22.3, respec tively. The entire sequence of two pseudogenes demonstrates the absenc e of introns, the presence of the 5' untranslated region of the cDNA, a 3' poly(A) tail, and the lack of sequence similarity with untranscri bed regions of the gene. The five pseudogenes are highly homologous to the cDNA, but contain a variable number of mutations that would produ ce mutated or truncated MIF-like proteins. Phylogenetic analyses of MI F genes and pseudogenes indicate several independent genetic events th at can account for multiple genomic integrations. Three of the Mif pse udogenes were also mapped by interspecific backcross to chromosomes 1, 9, and 17. These results suggest that Mif pseudogenes originated by r etrotransposition (C) 1995 Academic Press, Inc.