title: Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1.
abstract: 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.
authors.affiliation: Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, Via Olgettina 58, I-20132 Milan, Italy. incerti@tigem.it
authors.forename: B
authors.initials: B
authors.lastname: Incerti
authors.forename: K
authors.initials: K
authors.lastname: Cortese
authors.forename: A
authors.initials: A
authors.lastname: Pizzigoni
authors.forename: E M
authors.initials: EM
authors.lastname: Surace
authors.forename: S
authors.initials: S
authors.lastname: Varani
authors.forename: M
authors.initials: M
authors.lastname: Coppola
authors.forename: G
authors.initials: G
authors.lastname: Jeffery
authors.forename: M
authors.initials: M
authors.lastname: Seeliger
authors.forename: G
authors.initials: G
authors.lastname: Jaissle
authors.forename: D C
authors.initials: DC
authors.lastname: Bennett
authors.forename: V
authors.initials: V
authors.lastname: Marigo
authors.forename: M V
authors.initials: MV
authors.lastname: Schiaffino
authors.forename: C
authors.initials: C
authors.lastname: Tacchetti
authors.forename: A
authors.initials: A
authors.lastname: Ballabio
mesh_terms: D016117:Albinism, Ocular / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D018390:Gene Targeting; D005829:Geniculate Bodies / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D017496:Hypopigmentation; D008027:Light; D020460:Melanosomes / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009897:Optic Chiasm / Q000002:abnormalities / Q000473:pathology; D010857:Pigment Epithelium of Eye / Q000002:abnormalities / Q000196:embryology / Q000473:pathology / Q000648:ultrastructure; D013234:Stem Cells
chemical_list: D005136:Eye Proteins; C095276:GPR143 protein, human; D008562:Membrane Glycoproteins