Human dopamine transporter gene: variation and transcriptional regulation
Human dopamine transporter gene: variation and transcriptional regulation
批准号:
10472586
负责人:
Zhicheng Carl Lin
金额:
$41.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2007
资助国家:
美国
项目状态:
未结题
起止时间:
2007-09-01 至 2025-07-31
关键词:
AffectAlcohol consumptionAllelesAttentionAttention deficit hyperactivity disorderAutopsyBehavioralBindingBipolar DisorderBrainBrain DiseasesCellsCocaineCocaine use disorderCognitionComplementary DNAComplexConsensusCultured CellsDNA SequenceDevelopmentDiseaseDopamineDoseEndogenous FactorsEnhancersEukaryotic Initiation FactorsExogenous FactorsExonsGene ExpressionGenesGenetic PolymorphismGenetic Predisposition to DiseaseGenetic TranscriptionGenetic studyGoalsHaplotypesHormonesHumanIn VitroIndividualIntronsKnowledgeLeadLocomotionMediatingMental DepressionMidbrain structureMinisatellite RepeatsMolecularMolecular GeneticsMotivationMusNational Institute of Drug AbuseNuclearNucleotidesParkinson DiseasePathogenicityPatientsPlasmidsPlayPost-Traumatic Stress DisordersPrecision therapeuticsProteinsRNARegulationResearchRiskRisk FactorsRoleSchizophreniaShort-Term MemorySideSignal PathwaySiteSourceStressSubstance Use DisorderTestingTimeTranscription Initiation SiteTranscriptional RegulationUntranslated RegionsValidationVariantantagonistbasecis acting elementcocaine self-administrationdopamine transporterexperimental studyhybrid genein vivoknockout geneneuropsychiatric disorderneurotransmissionnovelpreventprogramspromoterprotective factorsprotein complexreuptakespatiotemporalsubstance usetranscription factortransmission process
中文摘要
这个更新建议的总体目标是剖析人类的遗传转录机制
英文摘要
The overall goal of this renewal proposal is to dissect genetic transcription mechanisms in the human
dopamine transporter gene (hDAT). The dopamine transporter (DAT) regulates the spatio-temporal domains of
dopamine neurotransmission by reuptake and release of dopamine and thus contributes to locomotion,
motivation, cognition and attention, working memory, behavioral organization and hormone release. It is well
recognized that expression of the DAT gene in the brain is highly circumscribed, varies among individual
subjects and can be regulated by endogenous and exogenous factors such as substance uses and stress.
Altered DAT expression may contribute to hDAT-associated pathophysiological states such as substance use
disorders (SUDs). However, information about how hDAT expression is regulated and how DNA sequence
variation influences the regulated expression remains largely sporadic. The hypothesis to be tested in this
proposal is that novel transcription factors (TFs) play a major role in regulating the hDAT promoter via disorder-
associated cis-acting sites. Our preliminary studies show that TFs may regulate the hDAT promoter in an
interactive manner. Therefore, three specific aims of this project are to: 1) demonstrate a RNA-protein complex
involved in the promoter regulation; 2) confirm a TF-mediated antagonism between 5’ and 3’ cis-acting sites;
and 3) identify TFs that bind to two functional VNTRs for promoter regulation. The results will add fundamental
knowledge on lead sites through which hDAT is regulated by signaling pathways and confers risks for related
brain disorders.
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Ventral midbrain correlation between genetic variation and expression of the dopamine transporter gene in cocaine-abusing versus non-abusing subjects.
可卡因滥用者与非滥用者的遗传变异与多巴胺转运蛋白基因表达之间的腹中脑相关性。
DOI:
10.1111/j.1369-1600.2011.00391.x
发表时间:
2014
期刊:
Addiction biology
影响因子:
3.4
作者:
[Zhou,Yanhong, Michelhaugh,SharonK, Schmidt,CarlJ, Liu,JunS, Bannon,MichaelJ, Lin,Zhicheng]
通讯作者:
Lin,Zhicheng
DOI:
10.1016/j.pnpbp.2010.11.001
发表时间:
2011-07-01
期刊:
Progress in neuro-psychopharmacology & biological psychiatry
影响因子:
5.6
作者:
[Xu M, Lin Z]
通讯作者:
Lin Z
DOI:
10.2217/pgs.13.141
发表时间:
2013-09
期刊:
Pharmacogenomics
影响因子:
2.1
作者:
[Zhao Y, Xiong N, Liu Y, Zhou Y, Li N, Qing H, Lin Z]
通讯作者:
Lin Z
DOI:
10.1038/s41598-017-17796-y
发表时间:
2017-12-12
期刊:
Scientific reports
影响因子:
4.6
作者:
[Liu QR, Canseco-Alba A, Zhang HY, Tagliaferro P, Chung M, Dennis E, Sanabria B, Schanz N, Escosteguy-Neto JC, Ishiguro H, Lin Z, Sgro S, Leonard CM, Santos-Junior JG, Gardner EL, Egan JM, Lee JW, Xi ZX, Onaivi ES]
通讯作者:
Onaivi ES
DOI:
10.1016/b978-0-12-385506-0.00001-6
发表时间:
2011
期刊:
PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE
影响因子:
--
作者:
[Lin, Zhicheng, Canales, Juan J., Bjoergvinsson, Throestur, Thomsen, Morgane, Qu, Hong, Liu, Qing-Rong, Torres, Gonzalo E., Caine, S. Barak]
通讯作者:
Caine, S. Barak
共 17 条
Monitoring DAT in Live Rats
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批准号:8440730
-
项目类别:
-
资助金额:$18.96万
-
财政年份:2012
-
负责人:Zhicheng Carl Lin
-
依托单位:
Monitoring DAT in Live Rat
-
批准号:8322983
-
项目类别:
-
资助金额:$19.75万
-
财政年份:2012
-
负责人:Zhicheng Carl Lin
-
依托单位:
Human Dopamine Transporter Gene: Variation and Transcriptional Regulation
-
批准号:8675815
-
项目类别:
-
资助金额:$24.89万
-
财政年份:2007
-
负责人:Zhicheng Carl Lin
-
依托单位:
Human dopamine transporter gene: variations and transcriptional regulation
-
批准号:7491627
-
项目类别:
-
资助金额:$31.56万
-
财政年份:2007
-
负责人:Zhicheng Carl Lin
-
依托单位:
Human dopamine transporter gene: variations and transcriptional regulation
-
批准号:7619951
-
项目类别:
-
资助金额:$31.56万
-
财政年份:2007
-
负责人:Zhicheng Carl Lin
-
依托单位:
Human dopamine transporter gene: variations and transcriptional regulation
-
批准号:7816807
-
项目类别:
-
资助金额:$31.24万
-
财政年份:2007
-
负责人:Zhicheng Carl Lin
-
依托单位:
Human dopamine transporter gene: variation and transcriptional regulation
-
批准号:9815162
-
项目类别:
-
资助金额:$41.0万
-
财政年份:2007
-
负责人:Zhicheng Carl Lin
-
依托单位:
Human dopamine transporter gene: variation and transcriptional regulation
-
批准号:10226304
-
项目类别:
-
资助金额:$41.0万
-
财政年份:2007
-
负责人:Zhicheng Carl Lin
-
依托单位:
Human dopamine transporter gene: variations and transcriptional regulation
-
批准号:8054967
-
项目类别:
-
资助金额:$30.93万
-
财政年份:2007
-
负责人:Zhicheng Carl Lin
-
依托单位:
Human Dopamine Transporter Gene: Variation and Transcriptional Regulation
-
批准号:8505959
-
项目类别:
-
资助金额:$24.89万
-
财政年份:2007
-
负责人:Zhicheng Carl Lin
-
依托单位:
Human dopamine transporter gene: variations and transcriptional regulation
-
批准号:7207906
-
项目类别:
-
资助金额:$32.2万
-
财政年份:2007
-
负责人:Zhicheng Carl Lin
-
依托单位:
海外基金