THE GENOMIC STRUCTURE AND CHROMOSOMAL LOCALIZATION OF THE MOUSE STAT3GENE

A variety of cytokines induce the tyrosine phosphorylation of signal t ransducers and activators of transcription (STATs), Activation of the same STAT proteins by distinct cytokines and activation of different S TAT proteins by each cytokine are thought to contribute to redundancy and pleiotropy of cytokine actions respectively, STAT3 is rapidly tyro sine phosphorylated in response to IL-6, ciliary neurotrophic factor, oncostatin M, leukemia inhibitory factor, IL-ll, granulocyte colony st imulation factor and epidermal growth factor, In this report we have i solated and characterized the mouse genomic structure of STAT3, The mo use STAT3 gene consisted of 24 exons which spanned >37 kb. The structu re of the mouse STAT3 gene was almost identical to that of the human S TAT2 gene, including the number and size of exons, indicating that the exon-intron organization had already been accomplished before these t wo genes duplicated, and then these genes evolved to respond to differ ent ligands. By molecular linkage analysis with interspecific backcros s mice the STAT3 gene mapped at 1.4 cM proximal to D11Mit59 on mouse c hromosome 11, The promoter region contained potential regulatory eleme nts such as GATA, NF-IL-6, PEBP2, Sp-1, AP-2 binding sites, cAMP respo nse element, CAAT box and E-box, Transient expression of constructs ha rboring the 5' flanking region of the STAT3 gene fused to the lucifera se gene showed that a 160 bp sequence upstream of the transcription st art site conferred a basal and an IL-6-inducible promoter activity.