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C. M. S. Daly, J. M. Gross; Zebrafish snow white as a Model for Oculocutaneous Albinism Disorders. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3670.
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Defects in the formation or function of lysosome-related organelles (LROs) are observed in several human albinism disorders, including Chediak-Higashi Syndrome, Hermansky-Pudlak Syndrome and Griscelli Syndrome. While much has been learned about the phenotypic characteristics and the genetic loci involved in these disorders, the molecular and cellular mechanisms underlying many of them remain to be elucidated. Melanosomes are a commonly studied LRO, as they are easy to identify and their biogenesis has been well described. The purpose of this study was to establish the zebrafish snow white (snw) mutant as a model to study the molecular and cellular underpinnings of ocular albinism.
Histology and transmission electron microscopy were utilized to examine the gross morphological and ultrastructural defects in the snw eye. Melanin levels were biochemically quantified, and linkage mapping and candidate gene sequencing were utilized to identify the mutated locus in snw. Gene expression markers for melanophores and iridophores were assayed by in situ hybridization in both snw and wild-type siblings.
The snw eye is microphthalmic but morphologically normal. snw mutants display oculocutaneous hypopigmentation in both their melanophores and iridophores by 48 hpf, continuing through 7 dpf. snw embryos show decreased total melanin in both the eye and whole body as compared to wild-type siblings; both melanophore and iridophore populations show decreased overall pigmentation. The mutation was mapped to a small region of chromosome 25; genes in the region were sequenced and investigated as candidate mutated loci.
The snw mutant posseses ocular defects similar to those observed in human albinism patients displaying Hermansky-Pudlak Syndrome. We demonstrate the usefulness of snw as a model to study melanosome biogenesis in the retinal pigmented epithelium and more generally as model for the formation, trafficking and function of lysosome-related organelles.
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