The Role SVOP in Neurotransmission

描述（由申请人提供）：神经递质释放的精确控制是由突触特异性蛋白质介导的。SV2是一个重要的调节因子家族，这是一个转运蛋白家族，已经成为治疗神经系统疾病的新疗法的目标。突触囊泡还含有一种相关蛋白，sv2样蛋白（SVOP），对其知之甚少。为了研究SVOP在神经传递中的作用，我们建议建立可以普遍或选择性地破坏SVOP表达的小鼠系。这些小鼠将成为确定SVOP如何促进神经元功能以及它是否有希望开发新疗法的关键试剂。

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.