The Role SVOP in Neurotransmission

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DESCRIPTION (provided by applicant): The precise control of neurotransmitter release is mediated by proteins specific to synapses. One family of essential regulators is SV2, a family of transporter-like proteins that have emerged as a target of new therapies to treat nervous system disorders. Synaptic vesicles also contain a related protein, SVOP (SV2-like protein), about which very little is known. To study the role of SVOP in neurotransmission, we propose to establish mouse lines in which SVOP expression can be universally or selectively disrupted. These mice will be a crucial reagent in determining both how SVOP contributes to neuronal functioning and whether it holds promise in the development of new therapeutics. PUBLIC HEALTH RELEVANCE: This pilot project will generate a genetically modified mouse line that will be used to identify the function of SVOP, a transporter-like protein present on synaptic vesicles about which very little is known. SVOP has significant similarity to SV2, a small family of synaptic vesicle proteins that are essential regulators of neurotransmitter release. SV2A is the binding site of a new class of antiepileptic drugs that are also finding use in the treatment of other nervous system disorders including neuropathic pain and dyskinesias. The proposed mouse line will play a crucial role in vetting SVOP's potential as an alternate drug target.