Transgenic and knockout approaches to study protocadherin function
研究原钙粘蛋白功能的转基因和敲除方法
基本信息
- 批准号:8547843
- 负责人:
- 金额:$ 18.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-19 至 2015-07-31
- 项目状态:已结题
- 来源:
- 关键词:Autistic DisorderAutomobile DrivingBehaviorBiological ModelsBrainBrain DiseasesBrain regionCadherinsCell ProliferationCell Surface ReceptorsCell physiologyCellsCollectionComplexDataDefectDevelopmentDevelopmental ProcessDiseaseDistributed SystemsEmbryoEnhancersEpilepsyEtiologyFamilyFemaleFoundationsFunctional disorderGene Transfer TechniquesGenesGeneticGenomeGerm-Line MutationGoalsHealthHumanImageIncidenceInfantKnock-outKnowledgeLabelLarvaLeadLesionLightMediatingMental RetardationMicroscopyModelingMolecularMutationNervous system structureNeuritesNeurodevelopmental DisorderNeuronsNeurosciencesPatternPhenotypePhotonsPositioning AttributeProcessReagentRegulatory ElementRetinaRoleSchizophreniaStereotypingSurveysTechnologyTestingTimeTransgenesTransgenic OrganismsVisual system structureWorkZebrafishZinc Fingersautism spectrum disorderaxon guidancebasecell motilityin vivoinsightmigrationmutantnervous system developmentneural circuitneurodevelopmentneuronal cell bodyneuronal patterningnucleasepromoterrelating to nervous systemself assemblysuperior colliculus Corpora quadrigeminasynaptogenesis
项目摘要
DESCRIPTION (provided by applicant): The development of the vertebrate brain requires complex genetic networks to coordinate myriad processes across time and space, which include cell proliferation, differentiation and migration, along with axon guidance, synapse formation and elimination. Orchestration of these processes results in the assembly of microcircuitry and distributed systems that constitute a functional nervous system. Disruptions in neural development can have a dramatic impact, resulting in complex brain disorders, such as autism spectrum disorders, schizophrenia, mental retardation and epilepsy. Increasingly, genetic data implicate genes involved in axon guidance and synaptogenesis in these complex brain disorders. In addition, evidence suggests a common etiology for these disorders, as mutations associated with one disorder are also associated with increased incidence of others. Among the molecules that have been implicated in these complex brain disorders are the protocadherins. In particular, mutations in pcdh19 result in a female-limited form of infant-onset epilepsy. Despite the clear role for these molecules in neural development and the etiology of neurodevelopmental dysfunction, relatively little is known about their function in vivo. Here, we propose to generate lines of zebrafish in which pcdh7a, pcdh9, pcdh17 and pcdh19 have been inactivated using zinc finger nucleases (ZFNs). In addition, we propose to generate BAC transgenic lines expressing GFP under the control of the pcdh7a, pcdh9, pcdh17 and pcdh19 regulatory elements. To study the effects of the protocadherin mutations on neural development, we will cross the GFP lines into the mutant backgrounds and use in vivo 2-photon microscopy to determine the impact of the mutations on nervous system development. This work will significantly advance our understanding of protocadherin function, providing a foundation for more mechanistic studies and facilitating a better understanding of how disruption of protocadherins can lead to complex brain disorders.
描述(由申请人提供):脊椎动物脑的发育需要复杂的遗传网络来协调跨越时间和空间的无数过程,其包括细胞增殖、分化和迁移,以及沿着轴突引导、突触形成和消除。这些过程的演示导致微电路和分布式系统的组装,构成功能神经系统。神经发育的中断会产生巨大的影响,导致复杂的大脑疾病,如自闭症谱系障碍、精神分裂症、智力迟钝和癫痫。越来越多的遗传数据表明,在这些复杂的大脑疾病中,基因参与了轴突导向和突触发生。此外,有证据表明这些疾病的共同病因,因为与一种疾病相关的突变也与其他疾病的发病率增加相关。在这些复杂的大脑疾病中涉及的分子是原钙粘蛋白。特别是,pcdh19基因突变导致女性局限性的婴儿癫痫。尽管这些分子在神经发育和神经发育功能障碍的病因学中具有明确的作用,但对其在体内的功能知之甚少。在这里,我们建议产生线的斑马鱼,其中pcdh7a,pcdh9,pcdh17和pcdh19已被灭活使用锌指核酸酶(ZFN)。此外,我们建议产生BAC转基因株系,表达GFP的控制下的pcdh7a,pcdh9,pcdh17和pcdh19调节元件。为了研究原钙粘蛋白突变对神经发育的影响,我们将GFP细胞系交叉到突变背景中,并使用体内双光子显微镜来确定突变对神经系统发育的影响。这项工作将大大推进我们对原钙粘蛋白功能的理解,为更多的机制研究提供基础,并促进更好地了解原钙粘蛋白的破坏如何导致复杂的大脑疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JAMES DAVID JONTES其他文献
JAMES DAVID JONTES的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JAMES DAVID JONTES', 18)}}的其他基金
The role of Protocadherin-17 in the development of direction selective circuits in the zebrafish visual system
Protocadherin-17 在斑马鱼视觉系统方向选择电路发育中的作用
- 批准号:
10582919 - 财政年份:2023
- 资助金额:
$ 18.3万 - 项目类别:
Protocadherin control of cell proliferation and differentiation
原钙粘蛋白控制细胞增殖和分化
- 批准号:
10390347 - 财政年份:2021
- 资助金额:
$ 18.3万 - 项目类别:
Protocadherin control of cell proliferation and differentiation
原钙粘蛋白控制细胞增殖和分化
- 批准号:
10799160 - 财政年份:2021
- 资助金额:
$ 18.3万 - 项目类别:
Protocadherin control of cell proliferation and differentiation
原钙粘蛋白控制细胞增殖和分化
- 批准号:
10591493 - 财政年份:2021
- 资助金额:
$ 18.3万 - 项目类别:
Protocadherin control of cell proliferation and differentiation
原钙粘蛋白控制细胞增殖和分化
- 批准号:
10185073 - 财政年份:2021
- 资助金额:
$ 18.3万 - 项目类别:
Protocadherins in zebrafish visual system development
原钙粘蛋白在斑马鱼视觉系统发育中的作用
- 批准号:
9767214 - 财政年份:2016
- 资助金额:
$ 18.3万 - 项目类别:
Protocadherins in zebrafish visual system development
原钙粘蛋白在斑马鱼视觉系统发育中的作用
- 批准号:
9159550 - 财政年份:2016
- 资助金额:
$ 18.3万 - 项目类别:
Mechanism of differential adhesion by protocadherin-cadherin complexes
原钙粘蛋白-钙粘蛋白复合物的差异粘附机制
- 批准号:
8359953 - 财政年份:2012
- 资助金额:
$ 18.3万 - 项目类别:
Transgenic and knockout approaches to study protocadherin function
研究原钙粘蛋白功能的转基因和敲除方法
- 批准号:
8430625 - 财政年份:2012
- 资助金额:
$ 18.3万 - 项目类别:
Mechanism of differential adhesion by protocadherin-cadherin complexes
原钙粘蛋白-钙粘蛋白复合物的差异粘附机制
- 批准号:
8472540 - 财政年份:2012
- 资助金额:
$ 18.3万 - 项目类别:
相似海外基金
Establishment of a method for evaluating automobile driving ability focusing on frontal lobe functions and its application to accident prediction
以额叶功能为中心的汽车驾驶能力评价方法的建立及其在事故预测中的应用
- 批准号:
20K07947 - 财政年份:2020
- 资助金额:
$ 18.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Evaluation of the Effectiveness of Multi-Professional Collaborative Assessment of Cognitive Function and Automobile Driving Skills and Comprehensive Support
认知功能与汽车驾驶技能多专业协同评估效果评价及综合支持
- 批准号:
17K19824 - 财政年份:2017
- 资助金额:
$ 18.3万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Development of Flexible Automobile Driving Interface for Disabled People
残疾人灵活汽车驾驶界面开发
- 批准号:
25330237 - 财政年份:2013
- 资助金额:
$ 18.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Automobile driving among older people with dementia: the effect of an intervention using a support manual for family caregivers
患有痴呆症的老年人的汽车驾驶:使用家庭护理人员支持手册进行干预的效果
- 批准号:
23591741 - 财政年份:2011
- 资助金额:
$ 18.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)