Drosophila Models of Human Disease

Sanhueza M, Chai A, Smith C, McCray BA, Simpson TI, Taylor JP, Pennetta G. Network Analyses Reveal Novel Aspects of ALS Pathogenesis. PLoS Genet. 2015 Mar 31;11(3):e1005107. PMID: 25826266.

Sanhueza et al. Fig. 2

From the abstract: "Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease ... Mutations in the human VAMP-associated protein B (hVAPB) cause a heterogeneous group of motor neuron diseases including ALS8. Despite extensive research, the molecular mechanisms underlying ALS pathogenesis remain largely unknown. Genetic screens for key interactors of hVAPB activity in the intact nervous system, however, represent a fundamental approach towards understanding the in vivo function of hVAPB and its role in ALS pathogenesis. Targeted expression of the disease-causing allele leads to neurodegeneration and progressive decline in motor performance when expressed in the adult Drosophila, eye or in its entire nervous system, respectively. By using these two phenotypic readouts, we carried out a systematic survey of the Drosophila genome to identify modifiers of hVAPB-induced neurotoxicity. ... Collectively, these results not only lead to a better understanding of hVAPB function but also point to potentially relevant targets for therapeutic intervention."