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

• Published in: Human molecular genetics 2000-11, Vol.9 (19), p.2781-2788
• Main Authors: INCERTI, Barbara, CORTESE, Katia, MARIGO, Valeria, SCHIAFFINO, Maria Vittoria, TACCHETTI, Carlo, BALLABIO, Andrea, PIZZIGNOI, Alessandro, SURACE, Enrico M, VARANI, Simona, COPPOLA, Massimiliano, JEFFERY, Glen, SEELIGER, Mathias, JAISSLE, Gesine, BENNETT, Dorothy C
• Format: Article
• Language: English
• Subjects: Albinism, Ocular - genetics; Albinism, Ocular - pathology; Aminoacid disorders; Animals; Biological and medical sciences; Cloning, Molecular; Disease Models, Animal; Electroretinography; Errors of metabolism; Eye Proteins - genetics; Eye Proteins - physiology; Gene Deletion; Gene Targeting; Geniculate Bodies - pathology; Histocytochemistry; Humans; Hypopigmentation; Light; Medical sciences; melanosomes; Melanosomes - genetics; Melanosomes - pathology; Melanosomes - ultrastructure; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Metabolic diseases; Mice; Mice, Inbred Strains; Mice, Knockout; Microscopy, Electron; ocular albinism; Optic Chiasm - abnormalities; Optic Chiasm - pathology; Pigment Epithelium of Eye - abnormalities; Pigment Epithelium of Eye - embryology; Pigment Epithelium of Eye - pathology; Pigment Epithelium of Eye - ultrastructure; retinal pigment epithelium; Stem Cells
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/9.19.2781

Ocular albinism type I (OA1) is an X-linked disorder characterized by severe reduction of visual acuity, strabismus, photophobia and nystagmus. Ophthalmologic examination reveals hypopigmentation of the retina, foveal hypoplasia and iris translucency. Microscopic examination of both retinal pigment epithelium (RPE) and skin melanocytes shows the presence of large pigment granules called giant melanosomes or macromelanosomes. In this study, we have generated and characterized Oa1-deficient mice by gene targeting (KO). The KO males are viable, fertile and phenotypically indistinguishable from the 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 pathway, demonstrating a misrouting of the optic fibres at the chiasm, as observed in OA1 patients. Microscopic examination of the RPE shows the presence of giant melanosomes comparable with those described in OA1 patients. Ultrastructural analysis of the RPE cells, suggests that the giant melanosomes may form by abnormal growth of single melanosomes, rather than the fusion of several, shedding light on the pathogenesis of ocular albinism.