| First Author | Shepard AR | Year | 2007 |
| Journal | Hum Mol Genet | Volume | 16 |
| Issue | 6 | Pages | 609-17 |
| PubMed ID | 17317787 | Mgi Jnum | J:121699 |
| Mgi Id | MGI:3711362 | Doi | 10.1093/hmg/ddm001 |
| Citation | Shepard AR, et al. (2007) Glaucoma-causing myocilin mutants require the Peroxisomal targeting signal-1 receptor (PTS1R) to elevate intraocular pressure. Hum Mol Genet 16(6):609-17 |
| abstractText | Glaucoma is a leading cause of worldwide irreversible visual impairment and blindness and is a clinically and genetically heterogeneous group of optic neuropathies. Specific mutations in the myocilin (MYOC) gene cause primary open angle glaucoma (POAG) with varying age-of-onset and degree of severity. We show a mutation-dependent, gain-of-function association between human myocilin and the peroxisomal targeting signal type 1 receptor (PTS1R). There was correlation between the glaucoma phenotype and the specific MYOC mutations, with the more severe early-onset POAG mutations having a higher degree of association with PTS1R. Expression of human myocilin glaucomatous mutations in mouse eyes causes elevated intraocular pressure, which is a major phenotype of MYOC glaucoma. This is the first demonstration of a disease resulting from mutation-induced exposure of a cryptic signaling site that causes mislocalization of mutant protein to peroxisomes and the first disease-gene-based animal model of human POAG. |
