CHARACTERIZATION OF THE MOUSE MYOC TIGR GENE

Mutations in the myocilin (MYOC), also known as Trabecular meshwork-In ducible Glucocorticoid Response (TIGR) gene can lead to juvenile open- angle glaucoma in human and may be responsible for at least 3% of prim ary open-angle glaucoma. To develop a mouse model of primary open angl e glaucoma, and to get deeper insight into the mechanisms of the MYOC/ TIGR gene regulation and function, we have isolated and characterized full size mouse Myoc/Tigr cDNA and genomic clones. The mouse and human MYOC/TIGR genes have the same exon-intron structure and contain 3 exo ns, although the mouse gene is 6 kb shorter than the human gene (10 kb versus 16 kb) due to differences in the length of introns. The MYOC/T IGR gene encodes a moderately conserved protein, which is 82% identica l between human and mouse. The encoded protein is 14 amino acids short er at the N-terminus in the mouse than in the human (490 versus 504 am ino acids). Mouse and human MYOC/TIGR genes show a similar pattern of expression in adult ocular and nonocular tissues. The mouse Myoc/Tigr gene was mapped to Chromosome 1 at position 82.8 cM from the centromer e. All residues, which were identified in the human MYOC/TIGR protein as critical for glaucoma development, are conserved in the mouse Myoc/ Tigr. (C) 1998 Academic Press.