Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1

Ocular albinism type I (OA1) is an X-linked disorder characterized by sever e reduction of visual acuity, strabismus, photophobia and nystagmus, Ophtha lmologic examination reveals hypopigmentation of the retina, foveal hypopla sia and iris translucency. Microscopic examination of both retinal pigment epithelium (RPE) and skin melanocytes shows the presence of large pigment g ranules called giant melanosomes or macromelanosomes, In this study, we hav e generated and characterized Oa1-deficient mice by gene targeting (KO), Th e KO males are viable, fertile and phenotypically indistinguishable from th e wild-type littermates. Ophthalmologic examination shows hypopigmentation of the ocular fundus in mutant animals compared with wild-type, Analysis of the retinofugal pathway reveals a reduction in the size of the uncrossed p athway, demonstrating a misrouting of the optic fibres at the chiasm, as ob served in OA1 patients. Microscopic examination of the RPE shows the presen ce of giant melanosomes comparable with those described in OAl patients. Ul trastructural analysis of the RPE cells, suggests that the giant melanosome s may form by abnormal growth of single melanosomes, rather than the fusion of several, shedding light on the pathogenesis of ocular albinism.