A new genetic tool for analyzing protocadherin diversity in mice

分析小鼠原钙粘蛋白多样性的新遗传工具

• 批准号: 8484468
• 负责人: XIAOZHONG ALEC WANG
• 金额: $ 7.45万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8484468
• 关键词: Affect; Afferent Neurons; Apoptosis; Axon; Biological Models; Brain; Cell surface; Cell-Cell Adhesion; Chromosome inversion; Complex; Data; Development; Developmental Process; Drosophila genus; Employee Strikes; Exhibits; Family; Gene Cluster; Genes; Genetic; Genetic Models; Genetic Recombination; Genomics; Hypothalamic structure; Interneurons; Investigation; Knock-out; Maintenance; Mammals; Measures; Mediating; Molecular; Morphology; Multiprotein Complexes; Mus; Mutant Strains Mice; Nervous system structure; Neuraxis; Neurologic; Neurons; Pathway interactions; Pattern; Phenotype; Play; Population; Protein Isoforms; Proteins; Proteomics; Resolution; Retinal Ganglion Cells; Role; Signal Transduction; Spinal; Surface; Synapses; System; Testing; Transgenic Mice; Zebrafish; base; design; mouse model; nestin protein; neural circuit; neurogenesis; neuron loss; neuronal circuitry; neuronal survival; protein complex; tool

DESCRIPTION (provided by applicant): The function of the brain relies on the precise assembly of approximately 100 billion neurons with trillions of synaptic connections. The development of neural circuitry involves a complex interplay of cell-cell adhesion, inter-neuronal signaling and assembly of intracellular macromolecular protein complexes. The three tandem-arrayed protocadherin (Pcdh) gene clusters, namely Pcdh-¿, Pcdh-¿ and Pcdh-?, regulate neuronal survival and synaptic development by distinct mechanisms. In this project, we will develop a new mouse genetic model to define the overlapping function of clustered Pcdhs in circuit development, independently from their role in neuronal survival. This line of investigation will advance our understanding of molecular diversity underlying the precision of neural circuitry in the brain.

描述（由申请人提供）：大脑的功能依赖于大约1000亿个神经元和数万亿个突触连接的精确组装。神经回路的发育涉及细胞间粘附、神经元间信号传导和细胞内大分子蛋白复合物组装等复杂的相互作用。三个串联排列的原钙粘蛋白（Pcdh）基因簇，即Pcdh-¿、Pcdh-¿和Pcdh-？，通过不同的机制调节神经元的存活和突触的发育。在这个项目中，我们将开发一个新的小鼠遗传模型来定义集群Pcdhs在电路发育中的重叠功能，而不是它们在神经元存活中的作用。这种调查方式