title: The zebrafish mutant vps18 as a model for vesicle-traffic related hypopigmentation diseases.
abstract: Hypopigmentation is a characteristic of several diseases associated with vesicle traffic defects, like the Hermansky-Pudlak, Chediak-Higashi, and Griscelli syndromes. Hypopigmentation is also a characteristic of the zebrafish mutant vps18(hi2499A), which is affected in the gene vps18, a component of the homotypic fusion and protein sorting complex that is involved in tethering during vesicular traffic. Vps18, as part of this complex, participates in the formation of early endosomes, late endosomes, and lysosomes. Here, we show that Vps18 is also involved in the formation of melanosomes. In the zebrafish mutant vps18(hi2499A) the retroviral insertion located at exon 4 of vps18, leads to the formation of two abnormal splicing variants lacking the coding sequence for the clathrin repeat and the RING finger conserved domains. A deficiency of Vps18 in zebrafish larvae results in hepatomegaly and skin hypopigmentation. We also observed a drastic reduction in the number of melanosomes in the eye's retinal pigmented epithelium along with the accumulation of immature melanosomes. A significant reduction in the vps18(hi2499A) larvae visual system capacity was found using the optokinetic response assay. We propose that the insertional mutant vps18(hi2499A) can be used as a model for studying hypopigmentation diseases in which vesicle traffic problems exist.
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, UNAM, Mexico DF, Mexico. emaldona@ifc.unam.mx
authors.forename: Ernesto
authors.initials: E
authors.lastname: Maldonado
authors.forename: Fabiola
authors.initials: F
authors.lastname: Hernandez
authors.forename: Carlos
authors.initials: C
authors.lastname: Lozano
authors.forename: Marta E
authors.initials: ME
authors.lastname: Castro
authors.forename: Rosa E
authors.initials: RE
authors.lastname: Navarro
mesh_terms: D000220:Adaptation, Biological; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D004625:Embryo, Nonmammalian; D006529:Hepatomegaly / Q000209:etiology; D017496:Hypopigmentation / Q000209:etiology / Q000235:genetics*; D008954:Models, Biological; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics*; D017120:Nystagmus, Optokinetic; D010641:Phenotype; D010802:Phylogeny; D010857:Pigment Epithelium of Eye / Q000002:abnormalities; D017354:Point Mutation; D020033:Protein Isoforms / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D022161:Transport Vesicles / Q000235:genetics / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D033921:Vesicular Transport Proteins; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D050505:Mutant Proteins; D020033:Protein Isoforms; D033921:Vesicular Transport Proteins; C504612:Vps18 protein, zebrafish; D029961:Zebrafish Proteins; D044767:Ubiquitin-Protein Ligases