Characterization and differential expression of a human gene family of olfactomedin-related proteins

Olfactomedin-related proteins are secreted glycoproteins with conserved C-t erminal motifs. Olfactomedin was originally identified as the major compone nt of the mucus layer that surrounds the chemosensory dendrites of olfactor y neurons. Homologues were subsequently found also in other tissues, includ ing the brain and in species ranging from Caenorhabditis elegans to Homo sa piens. Most importantly, the TIGR/myocilin protein, expressed in the eye an d associated with the pathogenesis of glaucoma, is an olfactomedin-related protein. The prevalence of olfactomedin-related proteins among species and their identification in different tissues prompted us to investigate whethe r a gene family exists within a species, specifically Homo sapiens. A GenBa nk search indeed revealed an entire human gene family of olfactomedin-relat ed proteins with at least five members, designated hOlfA through hOlfD and the TIGR/myocilin protein. hOlfA corresponds to the rat neuronal AMZ protei n. Phylogenetic analyses of 18 olfactomedin-related sequences resolved four distinct subfamilies. Among the human proteins, hOlfA and hOlfC, both expr essed in brain, are most closely related. Northern blot analyses of 16 huma n tissues demonstrated highly specific expression patterns: hOlfA is expres sed in brain, hOlfB in pancreas and prostate, hOlfC in cerebellum, hOlfD in colon, small intestine and prostate and TIGR/myocilin in heart and skeleta l muscle. The link between TIGR/myocilin and ocular hypertension and the ex pression of several of these proteins in mucus-lined tissues suggest that t hey play an important role in regulating physical properties of the extrace llular environment. Future studies can now assess whether other members of this gene family, like TIGR/myocilin, are also associated with human diseas e processes.