Functions of the FMRP Isoforms
Functions of the FMRP Isoforms
批准号:
7707256
负责人:
DAVID R MORRIS
金额:
$15.28万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-07-01 至 2009-06-30
关键词:
AcousticsAddressAnimalsBehaviorBehavioralBehavioral AssayBiochemicalBiologicalBiological AssayBiological ProcessBrainBrain regionCell ProliferationCharacteristicsChimeric ProteinsCollaborationsConditionDendritic SpinesEnd PointEpitopesFMR1 GeneFluorescenceFragile X Mental Retardation ProteinFragile X SyndromeHippocampus (Brain)IndividualKnock-in MouseKnock-outLong-Term DepressionLong-Term PotentiationMethodsMolecularMorphologyMusNeocortexNeuronsPartner in relationshipPerformancePhenotypePhysiologicalPreparationProcessPropertyProtein FamilyProtein IsoformsProteinsRNARNA BindingRecombinantsRoleSignal TransductionSocial DominanceSocial InteractionTestingTestisTranscriptUniversitiesVisualWashingtonWild Type Mousebasebehavior testknockout animalnerve stem cellneurophysiologyopen field behaviorresearch studysizetraffickingvector
中文摘要
项目II:大卫·莫里斯--华盛顿大学
FMRP异构体的功能
脆性X智力低下蛋白(FMRP)有多种异构体。这些异构体,
由Fmr1基因的初级转录本交替处理产生的,具有不同的
生化特性。因此,脆性X综合征(FXS)应该被认为不是由
缺乏单一的蛋白质,而是缺乏具有不同生物功能的蛋白质家族。一个
了解FMRP异构体的生物学作用显然对考虑治疗
条件。下面的具体目标是使用cDNA已经在其中的小鼠来解决这个问题
“敲入”Fmr1基因,产生只表达其中一种亚型的动物。四种选择
最初的研究是基于生物化学特性的丰富性和多样性。我们建议:
(I)确定表达单个FMRP亚型的小鼠表型的一般方面;(Ii)分析
重组小鼠的行为终点,以确定单个蛋白质之间的差异
异构体;(Iii)进行脑内长期增强和长期抑郁的神经生理学测试
先前已界定野生型动物与基因敲除动物差异的地区;及(Iv)
检测单个FMRP异构体在从神经元延伸的树突中的运输
从重组小鼠建立原代培养。
英文摘要
PROJECT II: DAVID MORRIS - UNIVERSITY OF WASHINGTON
FUNCTIONS OF THE FMRP ISOFORMS
There are multiple isoforms of the Fragile X Mental Retardation Protein (FMRP). These isoforms,
generated by alternative processing of the primary transcript from the Fmr1 gene, possess different
biochemical properties. Fragile X Syndrome (FXS) should therefore be considered to arise not from the
lack of a single protein, but from the absence of a family of proteins with different biological functions. An
understanding of the biological roles of the FMRP isoforms is clearly critical in considering treating for the
condition. The following specific aims address this question using mice in which cDNAs have been
"knocked in" the Fmr1 gene, yielding animals that express only one of the isoforms. The choice of four
isoforms for initial study was based on abundance and diversity of biochemical properties. We propose to:
(i) define general aspects of the phenotypes of mice expressing individual FMRP isoforms; (ii) assay
behavioral endpoints in the recombinant mice in order to define differences between the individual protein
isoforms; (iii) carry out neurophysiological tests of long-term potentiation and long-term depression in brain
regions where differences between wild-type and knockout animals have been previously defined; and (iv)
examine trafficking of the individual FMRP isoforms in dentritic processes extended from neurons in
primary cultures established from the recombinant mice.
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