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Janssens, K., Goethals, S., Atkinson, D., Ermanoska, B., Fransen, E., Jordanova, A., Auer-Grumbach, M., Asselbergh, B., Timmerman, V. (2014). Human Rab7 mutation mimics features of Charcot-Marie-Tooth neuropathy type 2B in Drosophila.  Neurobiol. Disease 65(): 211--219.
FlyBase ID
FBrf0224472
Publication Type
Research paper
Abstract

Charcot-Marie-Tooth disease type 2B (CMT2B) is an inherited axonal peripheral neuropathy. It is characterised by prominent sensory loss, often complicated by severe ulcero-mutilations of toes or feet, and variable motor involvement. Missense mutations in RAB7A, the gene encoding the small GTPase Rab7, cause CMT2B and increase Rab7 activity. Rab7 is ubiquitously expressed and is involved in degradation through the lysosomal pathway. In the neurons, Rab7 plays a role in the long-range retrograde transport of signalling endosomes in the axons. Here we developed the first animal model of CMT2B, modelling one of the mutations (L129F) in Drosophila melanogaster. Behavioural assays show that this model recapitulates several hallmarks of the human disease. Upon expression of mutant Rab7 in the sensory neurons, larvae present with a reduction of temperature and pain perception. Furthermore, the larvae exhibit a crawling defect when the mutant protein is expressed in the motor neurons. Analysis of axonal transport of Rab7 positive vesicles in sensory neurons of Drosophila larvae and in neurites of mammalian neuroblastoma cells demonstrates that mutant vesicles pause less than their wild-type counterparts. This latter finding indicates that alterations in vesicle transport might contribute to the pathomechanism of CMT2B.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Neurobiol. Disease
    Title
    Neurobiology of Disease
    Publication Year
    1994-
    ISBN/ISSN
    0969-9961
    Data From Reference
    Alleles (9)
    Genes (6)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (4)
    Experimental Tools (2)
    Transgenic Constructs (4)