Characterization of the murine TIGR/myocilin gene

There is a genetic predisposition to primary open-angle glaucoma, illustrated by a disease prevalence of 6% among first degree relatives of affected individuals, compared with a prevalence in the general population of less than 1%. Mutations in a gene located on Chromosome (Chr) 1q23-q24 have recently been shown to cause open-angle glaucoma in selected families and in 3% of sporadic cases. The gene was independently discovered by two groups and named trabecular meshwork induced glucocorticoid response (TIGR) gene, and myocilin (MYOC). (The nomenclature committees have approved MYOC and Myoc as the symbols for the human and mouse genes, respectively.) The ten glaucoma-associated TIGR/MYOC mutations described thus far (nine amino acid substitutions and a premature stop codon) all lie within the third exon of the gene. This exon is phylogenetically conserved and has similarity to olfactomedin, an extracellular matrix glycoprotein of unknown function that is an abundant constituent of the frog olfactory neuroepithelium. The function of the TIGR/MYOC protein is also unknown. TIGR/MYOC mRNA is expressed in ocular tissues (TM, ciliary body, sclera, and choroid), as well as non-ocular tissues (heart, skeletal muscle, mammary, thymus, and testis). With the aim of advancing understanding of the function of TIGR/MYOC and its role in glaucoma, we have cloned and characterized its murine ortholog. We used oligonucleotides based on human TIGR/MYOC cDNA sequence (GenBank accession no. U85257) and the polymerase chain reaction (PCR) to amplify sequences from mouse genomic DNA.