| First Author | Grishchuk Y | Year | 2016 |
| Journal | Am J Pathol | Volume | 186 |
| Issue | 1 | Pages | 199-209 |
| PubMed ID | 26608452 | Mgi Jnum | J:228205 |
| Mgi Id | MGI:5705667 | Doi | 10.1016/j.ajpath.2015.09.017 |
| Citation | Grishchuk Y, et al. (2016) Retinal Dystrophy and Optic Nerve Pathology in the Mouse Model of Mucolipidosis IV. Am J Pathol 186(1):199-209 |
| abstractText | Mucolipidosis IV is a debilitating developmental lysosomal storage disorder characterized by severe neuromotor retardation and progressive loss of vision, leading to blindness by the second decade of life. Mucolipidosis IV is caused by loss-of-function mutations in the MCOLN1 gene, which encodes the transient receptor potential channel protein mucolipin-1. Ophthalmic pathology in patients includes corneal haze and progressive retinal and optic nerve atrophy. Herein, we report ocular pathology in Mcoln1(-/-) mouse, a good phenotypic model of the disease. Early, but non-progressive, thinning of the photoreceptor layer, reduced levels of rhodopsin, disrupted rod outer segments, and widespread accumulation of the typical storage inclusion bodies were the major histological findings in the Mcoln1(-/-) retina. Electroretinograms showed significantly decreased functional response (scotopic a- and b-wave amplitudes) in the Mcoln1(-/-) mice. At the ultrastructural level, we observed formation of axonal spheroids and decreased density of axons in the optic nerve of the aged (6-month-old) Mcoln1(-/-) mice, which indicates progressive axonal degeneration. Our data suggest that mucolipin-1 plays a role in postnatal development of photoreceptors and provides a set of outcome measures that can be used for ocular therapy development for mucolipidosis IV. |
