Illuminating the functions of CACNA2D4 in the brain

阐明 CACNA2D4 在大脑中的功能

• 批准号: 9813213
• 负责人: AMY LEE
• 金额: $ 15.45万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9813213
• 关键词: Address; Affect; Affective; Animal Model; Antibodies; Anxiety; Behavior; Behavioral; Bipolar Disorder; Brain; CAV1 gene; Cell membrane; Cells; Cognitive; Complex; Defect; Disease; Epilepsy; Etiology; Failure; Future; Genes; Genetic; Genetic Transcription; Genetic study; Goals; Human Genetics; Immunohistochemistry; Impairment; In Situ Hybridization; Ion Channel Protein; Knockout Mice; Light; Maintenance; Mental Depression; Mission; Modeling; Mus; Mutation; Nervous system structure; Neurons; Neurophysiology - biologic function; Outcome; Outcomes Research; Patients; Phenotype; Play; Presynaptic Terminals; Process; Protein Family; Proteins; Research; Retina; Retinal Photoreceptors; Role; Schizophrenia; Shapes; Short-Term Memory; Signal Transduction; Site; Structure; Time; Variant; Vision; Visual; autism spectrum disorder; base; density; design; endophenotype; experimental study; extracellular; human disease; insight; knockout animal; loss of function; loss of function mutation; member; mouse model; neural circuit; neuropsychiatric disorder; neurotransmitter release; novel; painful neuropathy; polyclonal antibody; presynaptic; receptor; synaptogenesis; tool; voltage

Project Summary Variants in the genes that encode voltage-gated Ca2+ channels are consistently and robustly associated with schizophrenia, bipolar disorder, and autism spectrum disorder. One of these genes is CACNA2D4, an IDG-elibigle gene that encodes an extracellular Ca2+ channel subunit (2-4) expressed in both the brain and retina. In the case of the retina, it has been established that 2-4 is required for normal vision. By contrast, the role of this protein in the brain remains understudied; we known neither where in the brain it acts nor what functions it may have there. The long-term goal of this project is to understand how genetic alterations in Cav-channel contributes to the complex etiology of neuropsychiatric disorders. The overall objective of the proposed research is to establish the cellular distribution of 2-4 in the mouse brain and which behaviors are disrupted in mice lacking this protein. The specific aims are to (1) define the neural circuits that may be regulated by 2–4 in the mouse brain and (2) identify cognitive/affective phenotypes in 2-4 knock-out mice. To accomplish these aims, we will use antibodies against 2–4 in immunohistochemical analyses of mouse brain, and behavioral analyses designed to uncover alterations in cognitive or affective function in mice.

项目摘要 编码电压门控钙通道的基因的变异是始终如一且强劲的 与精神分裂症、双相情感障碍和自闭症谱系障碍有关。这其中的一个 基因是CACNA2D4，一个编码细胞外钙通道的IDG-eligigle基因 亚基(2，-4)在脑和视网膜中均有表达。就视网膜而言，它一直是 已确定正常视力需要2-4。相比之下，这种蛋白质在细胞内的作用 大脑仍然缺乏研究；我们既不知道它在大脑中的作用，也不知道它的功能是什么 可能就在那里。这个项目的长期目标是了解基因改变是如何 在Cav-通道中，神经精神障碍的复杂病因起着重要作用。整体而言 本研究的目的是建立-2-4在人卵巢癌组织中的细胞分布。 缺乏这种蛋白质的小鼠的大脑和哪些行为受到干扰。具体的 目的是(1)确定小鼠大脑中可能受2-4调控的神经回路 以及(2)确定2-4基因敲除小鼠的认知/情感表型。要实现这些目标 目的：我们将使用抗-2-4抗体对小鼠进行免疫组织化学分析。 大脑，以及旨在揭示认知或情感变化的行为分析 在小鼠身上起作用。