GENE STRUCTURE AND PROPERTIES OF TIGR, AN OLFACTOMEDIN-RELATED GLYCOPROTEIN CLONED FROM GLUCOCORTICOID-INDUCED TRABECULAR MESHWORK CELLS

Expression of the trabecular meshwork inducible glucocorticoid respons e (TIGR) gene progressively increases from barely detectable levels to greater than 2% of total cellular mRNA over 10 days exposure of trabe cular meshwork (TM) cells to dexamethasone. Cycloheximide blocked most of the TIGR mRNA induction, suggesting a requirement for ongoing prot ein synthesis. The genomic structure of TIGR (similar to 20 kilobases) consists of 3 exons, and a 5-kilobase promoter region that contains 1 3 predicted hormone response elements, including several glucocorticoi d regulatory elements, and other potentially important regulatory moti fs. TIGR cDNA encodes an olfactomedin-related glycoprotein of 504 amin o acids with motifs for N- and O-linked glycosylation, glycosaminoglyc an initiation, hyaluronic acid binding, and leucine zippers. Recombina nt TIGR (rTIGR) showed oligomerization and specific binding to TM cell s. Anti-rTIGR antibody detected multiple translational/post-translatio nal forms of TIGR produced by the cells (including secreted 66 kDa/55 kDa glycoproteins/proteins in the media and 55 kDa cellular proteins), whereas Northern blot showed a single mRNA species. The findings sugg est potential mechanisms by which TIGR could obstruct the aqueous humo r fluid flow and participate in the pathogenesis of glaucoma.