1-National Reserach Centre «B.P. Konstantinov PNPI», Gatchina, Russia;
2-Ivan Franko National University of L'viv, L'viv, Ukraine
NTE human gene is a molecular target for organophosphorus compound poisoning leading to the development of organophosphorus induced delayed neuropathy (OPIDN). NTE mutations lead to the development of the autosomal recessive form of the hereditary spastic paraplegia (HSP SPG39). Hereditary spastic paraplegia is a heterogenic group of the diseases leading to the development of the lower limb paralysis. Both HSP and OPIDN are characterized by the distal neurodegeneration of motor and sensitive axons. Pathological mechanisms
underlying the HSP and OPIDN development are poorly understood today despite the amount of research carried out on the subject. One of the main experimental solutions of studying the functions of human genes is to study their orthologs in model animals. swiss cheese (sws) is an ortholog of human NTE in Drosophila melanogaster. sws mutants are characterized by progressive neurodegeneration and glia disruption in a brain and early death of the adult animals.
To study swsfunctions we chose neuromuscular junctions (NMJs) of the 3rd instar larvae of Drosophila melanogaster, the system allowing analysis of changes in a single neuron. In this study we examined the sws mutants: sws1, sws4, 76-15, swsolfE. Using methods of genetics, immunohistochemistry and confocal microscopy we showed that sws plays an important role in processes of NMJs formation and functioning. Mutations in sws are shown to have altered the size and the number of big synaptic boutons and the number of the satellite boutons and caused abnormal distribution of synaptic proteins in NMJs of Drosophila melanogaster. Axonal transport analysis showed a severe alteration of mitochondrial clusters and synaptotagmin quantity in axons of sws mutant larvae.