PUBLICATION

The zebrafish mutant vps18 as a model for vesicle-traffic related hypopigmentation diseases

Authors
Maldonado, E., Hernandez, F., Lozano, C., Castro, M.E., and Navarro, R.E.
ID
ZDB-PUB-060719-7
Date
2006
Source
Pigment cell research   19(4): 315-326 (Journal)
Registered Authors
Maldonado, Ernesto
Keywords
none
MeSH Terms
  • Adaptation, Biological
  • Alternative Splicing/genetics
  • Amino Acid Sequence
  • Animals
  • Biological Transport/genetics
  • Embryo, Nonmammalian
  • Hepatomegaly/etiology
  • Hypopigmentation/etiology
  • Hypopigmentation/genetics*
  • Models, Biological
  • Molecular Sequence Data
  • Mutant Proteins/genetics*
  • Nystagmus, Optokinetic
  • Phenotype
  • Phylogeny
  • Pigment Epithelium of Eye/abnormalities
  • Point Mutation
  • Protein Isoforms/genetics
  • Sequence Homology, Amino Acid
  • Transport Vesicles/genetics
  • Transport Vesicles/pathology*
  • Ubiquitin-Protein Ligases/genetics*
  • Zebrafish
  • Zebrafish Proteins/genetics*
PubMed
16827750 Full text @ Pig. Cell Res.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping