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Tubulin Beta 4a in central nervous system development and disease

微管蛋白 Beta 4a 在中枢神经系统发育和疾病中的作用

基本信息

批准号：
9158393
负责人：
Karel F Liem
金额：
$ 42.98万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9158393
关键词：
Affect Alleles Amyotrophic Lateral Sclerosis Atrophic Axon Basal Ganglia Behavior Biological Biology CNS degeneration Cell Culture Techniques Cell physiology Cells Central Nervous System Diseases Cerebellum Collection Cytoskeleton Defect Degenerative Disorder Development Developmental Process Disease Dystonia Employee Strikes Functional disorder Genes Genetic Genetic Screening Genetic screening method In Vitro Individual Knock-in LacZ Genes Lead LoxP-flanked allele Methods Microcephaly Microtubules Missense Mutation Modeling Molecular Molecular Genetics Motor Movement Disorders Mus Mutant Strains Mice Mutation Nature Nervous System Physiology Neuraxis Neurons Neurophysiology - biologic function Oligodendroglia Pathology Patients Phenotype Point Mutation Process Property Reporting Research Role Series Subcellular structure Testing Therapeutic Tissues Transmission Electron Microscopy Tubulin base beta Tubulin cell type developmental disease disease phenotype disease-causing mutation genetic analysis granule cell human disease in vivo insight lissencephaly loss of function mammalian genome motor disorder mouse model mutant myelination nervous system development nervous system disorder neurodevelopment neurological pathology novel oculomotor

项目摘要

Nervous system development and function is critically dependent upon its microtubule-based cytoskeleton. Microtubules are assembled from multiple α- and ß-tubulin isotypes which are encoded by separate, evolutionarily conserved genes. Recently, mutations in the Tubulin ß4a (Tubb4a) have been associated with a spectrum of neurological disorders in patients by sequencing studies. How mutations in the Tubb4a gene cause these disorders is not understood. We have generated a mouse model for Tubb4a-related developmental disorders from a forward genetic screen. Our studies will lead to insights into the mechanisms of the human disease spectrum, as well as to fundamental information on the role of microtubules in mammalian neural development and function.

神经系统的发育和功能严重依赖于其基于微管的细胞骨架微管由多种α-和β-微管蛋白同种型组装而成，这些同种型由独立的进化保守基因最近，Tubulin β 4a（Tubb 4a）的突变已被发现。通过测序研究发现，与患者的神经系统疾病谱相关。基因突变 Tubb 4a基因导致这些疾病尚不清楚。我们已经生成了一个与Tubb 4a相关的小鼠模型，从遗传筛查中发现的发育障碍我们的研究将有助于深入了解人类疾病谱，以及微管的作用的基本信息，哺乳动物的神经发育和功能。