Illuminating the functions of CACNA2D4 in the brain

阐明 CACNA2D4 在大脑中的功能

基本信息

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
项目类别：
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

项目摘要

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Ca2+通道的基因中的变体始终如一与精神分裂症，躁郁症和自闭症谱系障碍有关。其中之一基因是CACNA2D4，它是一个编码细胞外Ca2+通道的IDG-晶状体基因亚基（2-4）在大脑和视网膜中均表达。在视网膜的情况下，确定正常视力需要2-4。相比之下，该蛋白在大脑仍然被理解；我们既不知道它在大脑中的位置，也不知道什么功能可能在那里。该项目的长期目标是了解遗传改变在CAV通道中，有助于神经精神疾病的复杂病因。总体拟议的研究的目的是建立2-4的细胞分布小鼠大脑以及缺乏该蛋白质的小鼠中的哪些行为被破坏。具体目的是（1）定义小鼠大脑中可能受2 -4调节的神经回路（2）在2-4敲除小鼠中识别认知/情感表型。完成这些目的，我们将在小鼠的免疫组织化学分析中使用针对2 -4的抗体大脑以及旨在发现认知或情感改变的行为分析小鼠的功能。