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
项目二:大卫·莫里斯-华盛顿大学
FMRP同构的函数
脆性X智力迟钝蛋白(FMRP)有多种亚型。这些异构体,
通过选择性加工来自Fmr 1基因的初级转录物产生的,具有不同的
生化特性因此,脆性X综合征(FXS)应被认为不是由
缺乏单一的蛋白质,而是缺乏具有不同生物学功能的蛋白质家族。一个
理解FMRP同种型的生物学作用对于考虑治疗FMRP亚型是至关重要的。
条件以下具体目的使用小鼠解决了这个问题,在小鼠中cDNA已经被表达。
“敲入”Fmr 1基因,产生的动物只表达其中一种亚型。四选一
用于初始研究的同种型是基于生物化学性质的丰度和多样性。我们建议:
(i)定义表达单个FMRP同种型的小鼠的表型的一般方面;(ii)测定
行为终点,以确定个体蛋白质之间的差异
亚型;(iii)进行脑中长时程增强和长时程抑制的神经生理学测试
野生型和敲除动物之间的差异先前已被定义的区域;和(iv)
检查从神经元延伸的树突状突起中单个FMRP同种型的运输,
从重组小鼠建立原代培养物。
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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