Development of a Novel Model for Tourettes Syndrome
Development of a Novel Model for Tourettes Syndrome
批准号:
8743424
负责人:
NICOLE CALAKOS
金额:
$23.55万
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
项目状态:
已结题
起止时间:
2012-02-01 至 2016-01-31
关键词:
AcuteAdultAffectAllelesAnabolismAnimal ModelAttention deficit hyperactivity disorderBehaviorBehavioralBiologyBrainC57BL/6 MouseClinicalCodeComorbidityConstitutionCorpus striatum structureDefectDevelopmentDiseaseES Cell LineEnzymesFathersFirst Degree RelativeFutureGene DeletionGene ProteinsGene-ModifiedGenesGeneticGenetic ModelsGenetic Predisposition to DiseaseGilles de la Tourette syndromeGoalsHeterozygoteHistamineHistidine DecarboxylaseHumanHuman GeneticsInheritance PatternsInheritedKnockout MiceLightMeasuresMediatingMessenger RNAModelingMouse ProteinMovement DisordersMusMutant Strains MiceMutationNonsense CodonNonsense MutationObsessive-Compulsive DisorderPartner in relationshipPathogenesisPatientsPenetrancePhasePhenotypePhysiologyPopulationPreclinical Drug EvaluationPreclinical TestingProteinsReagentRoleSiteSliceSpecificitySymptomsSynaptic TransmissionTestingTransgenic OrganismsTriad Acrylic ResinVariantbasebehavior testdisease mechanisms studydrug developmentembryonic stem cellextracellularmouse genomemouse modelmutantneurotransmissionnovelnovel therapeuticsoffspringprogramsprotein protein interactionrecombinasescreeningtransmission process
中文摘要
描述(由申请人提供):妥瑞氏综合征(TS)及其相关疾病(抽搐、强迫症、ADHD)构成了巨大的社会负担,因为据估计,仅TS就影响了近1%的人群。在理解这些疾病的机制方面取得进展的一个关键障碍是缺乏与人类疾病病因相关的动物模型。我们建议利用最近发现的TS的遗传病因,涉及组氨酸脱羧酶基因内的无义突变,以克服这一障碍。在这项提案中,我们将创建,验证和行为表征一种新的小鼠模型TS。为了最忠实地复制基于蛋白质的病理生物学,因为它发生在人类中,我们将创建“人源化”小鼠模型,表达人类蛋白质代替内源性小鼠蛋白质。此外,因为这样的模型将表达人TS突变体蛋白,一旦验证,该小鼠模型将独特地适合于以常规小鼠敲入方法所不能提供的方式筛选新的治疗剂。
英文摘要
DESCRIPTION (provided by applicant): Tourette Syndrome (TS) and its associated conditions (tics, OCD, ADHD) constitute a substantial societal burden, as TS alone is estimated to affect nearly 1% of the population. A critical barrier to progress in understanding the mechanisms for these disorders is the lack of animal models with etiological relevance to the human condition. We propose to take advantage of the recent discovery of a genetic etiology for TS involving a nonsense mutation within the histidine decarboxylase gene to overcome this barrier. In this proposal we will create, validate and behaviorally characterize a novel mouse model for TS. To most faithfully replicate the protein-based pathobiology as it occurs in humans, we will create "humanized" mouse models that express the human protein in place of the endogenous mouse protein. Moreover, because such a model will express the human TS mutant protein, once validated, this mouse model will be uniquely suited for screening novel therapeutics in a way that is not afforded by conventional mouse knockin approaches.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Significance of Protein Synthesis by the Integrated Stress Response in Neuromodulatory Neurons for Adaptive Behavior and Synaptic Plasticity
-
批准号:10718345
-
项目类别:
-
资助金额:$63.63万
-
财政年份:2023
-
负责人:NICOLE CALAKOS
-
依托单位:
Striatal Plasticity in Habit Formation as a Platform to Deconstruct Adaptive Learning
-
批准号:10451714
-
项目类别:
-
资助金额:$101.85万
-
财政年份:2018
-
负责人:NICOLE CALAKOS
-
依托单位:
Striatal Plasticity in Habit Formation as a Platform to Deconstruct Adaptive Learning
-
批准号:10207803
-
项目类别:
-
资助金额:$99.34万
-
财政年份:2018
-
负责人:NICOLE CALAKOS
-
依托单位:
Striatal Plasticity in Habit Formation as a Platform to Deconstruct Adaptive Learning
-
批准号:9789068
-
项目类别:
-
资助金额:$99.44万
-
财政年份:2018
-
负责人:NICOLE CALAKOS
-
依托单位:
Novel high-throughput screening for modifiers of TorsinA pathology
-
批准号:8517913
-
项目类别:
-
资助金额:$23.55万
-
财政年份:2013
-
负责人:NICOLE CALAKOS
-
依托单位:
Novel high-throughput screening for modifiers of TorsinA pathology
-
批准号:8634153
-
项目类别:
-
资助金额:$19.43万
-
财政年份:2013
-
负责人:NICOLE CALAKOS
-
依托单位:
Development of a Novel Model for Tourettes Syndrome
-
批准号:8215517
-
项目类别:
-
资助金额:$15.7万
-
财政年份:2012
-
负责人:NICOLE CALAKOS
-
依托单位:
Development of a Novel Model for Tourettes Syndrome
-
批准号:8415843
-
项目类别:
-
资助金额:$14.78万
-
财政年份:2012
-
负责人:NICOLE CALAKOS
-
依托单位:
Novel Genetic Mouse Model to Study the Consequences of TorsinA Dysfunction
-
批准号:8114531
-
项目类别:
-
资助金额:$23.08万
-
财政年份:2011
-
负责人:NICOLE CALAKOS
-
依托单位:
Novel Genetic Mouse Model to Study the Consequences of TorsinA Dysfunction
-
批准号:8287547
-
项目类别:
-
资助金额:$19.14万
-
财政年份:2011
-
负责人:NICOLE CALAKOS
-
依托单位:
Cortico-striatal synaptic defects and compulsive motor behaviors in mice
-
批准号:7302868
-
项目类别:
-
资助金额:$32.51万
-
财政年份:2008
-
负责人:NICOLE CALAKOS
-
依托单位:
Cortico-striatal synaptic defects and compulsive motor behaviors in mice
-
批准号:7623481
-
项目类别:
-
资助金额:$34.13万
-
财政年份:2008
-
负责人:NICOLE CALAKOS
-
依托单位:
Cortico-striatal synaptic defects and compulsive motor behaviors in mice
-
批准号:8117560
-
项目类别:
-
资助金额:$33.44万
-
财政年份:2008
-
负责人:NICOLE CALAKOS
-
依托单位:
Cortico-striatal synaptic defects and compulsive motor behaviors in mice
-
批准号:7814862
-
项目类别:
-
资助金额:$41.2万
-
财政年份:2008
-
负责人:NICOLE CALAKOS
-
依托单位:
Cortico-striatal neurotransmission and compulsive motor behaviors
-
批准号:8514180
-
项目类别:
-
资助金额:$34.1万
-
财政年份:2008
-
负责人:NICOLE CALAKOS
-
依托单位:
Cortico-striatal neurotransmission and compulsive motor behaviors
-
批准号:8687752
-
项目类别:
-
资助金额:$33.76万
-
财政年份:2008
-
负责人:NICOLE CALAKOS
-
依托单位:
Cortico-striatal neurotransmission and compulsive motor behaviors
-
批准号:8921283
-
项目类别:
-
资助金额:$34.1万
-
财政年份:2008
-
负责人:NICOLE CALAKOS
-
依托单位:
Cortico-striatal neurotransmission and compulsive motor behaviors
-
批准号:9327070
-
项目类别:
-
资助金额:$34.1万
-
财政年份:2008
-
负责人:NICOLE CALAKOS
-
依托单位:
Cortico-striatal synaptic defects and compulsive motor behaviors in mice
-
批准号:8318220
-
项目类别:
-
资助金额:$33.44万
-
财政年份:2008
-
负责人:NICOLE CALAKOS
-
依托单位:
Dynamic Regulation of Neurotransmitter Release
-
批准号:7472468
-
项目类别:
-
资助金额:$15.0万
-
财政年份:2006
-
负责人:NICOLE CALAKOS
-
依托单位:
海外基金