The zebrafish mutant lbk/vam6 resembles human multisystemic disorders caused by aberrant trafficking of endosomal vesicles

Schonthaler, H. B. and Fleisch, V. C. and Biehlmaier, O. and Makhankov, Y. and Rinner, O. and Bahadori, R. and Geisler, R. and Schwarz, H. and Neuhauss, S. C. F. and Dahm, R.. (2008) The zebrafish mutant lbk/vam6 resembles human multisystemic disorders caused by aberrant trafficking of endosomal vesicles. Development, 135 (2). pp. 387-399.

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The trafficking of intracellular vesicles is essential for a number of cellular processes and defects in this process have been implicated in a wide range of human diseases. We identify the zebrafish mutant lbk as a novel model for such disorders. lbk displays hypopigmentation of skin melanocytes and the retinal pigment epithelium (RPE), an absence of iridophore reflections, defects in internal organs (liver, intestine) as well as functional defects in vision and the innate immune system (macrophages). Positional cloning, an allele screen, rescue experiments and morpholino knock-down reveal a mutation in the zebrafish orthologue of the vam6/vps39 gene. Vam6p is part of the HOPS complex, which is essential for vesicle tethering and fusion. Affected cells in the lbk RPE, liver, intestine and macrophages display increased numbers and enlarged intracellular vesicles. Physiological and behavioural analyses reveal severe defects in visual ability in lbk mutants. The present study provides the first phenotypic description of a lack of vam6 gene function in a multicellular organism. lbk shares many of the characteristics of human diseases and suggests a novel disease gene for pathologies associated with defective vesicle transport, including the arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, the Hermansky-Pudlak syndrome, the Chediak-Higashi syndrome and the Griscelli syndrome.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Imaging Core Facility (Biehlmaier)
UniBasel Contributors:Biehlmaier, Oliver
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Company of Biologists
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:28 Nov 2017 10:36
Deposited On:28 Nov 2017 10:36

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