Several inherited human diseases [such as arthrogryposis-renal dysfunction-cholestasis and Hermansky-Pudlak (HP) syndromes] are associated with defective vesicle transport, which is an essential process for many cellular events. Now, Neuhauss, Dahm and colleagues identify the zebrafish mutant leberknödel (lbk) as a model for such disorders(see ). These mutants, like individuals with HP syndrome and similar disorders, have hypopigmented skin melanocytes and a hypopigmented retinal pigment epithelium(RPE). The mutant fish also have visual and immunological defects and defects in various internal organs. The researchers identify the mutation in lbk as a loss-of-function mutation in the gene encoding Vam6p/Vps39p,which is required for the trafficking of lysosomes and lysosome-related vesicles, such as melanosomes. They also report that macrophages and cells in the RPE, liver and intestines of lbk mutants contain increased numbers of enlarged intracellular vesicles compared with wild-type cells. Overall, these results highlight vam6 as a novel candidate disease gene and reveal its requirement for normal development for future research to explore.
