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Generation and characterization a conditional mouse model of Parkinson’s disease

Generation and characterization a conditional mouse model of...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Xian LIN,Hoon SHIM,Amy CHEN,Huaibin CAI Unit of Transgenesis,Laboratory of Neurogenetics,National Institute on Aging,National Institutes of Health,Bethesda, Maryland 20892,USA

＜正＞Degeneration of nigrostriatal dopaminergic neurons and formation of Lewy Bodies（LB） are two major pathological hallmarks of Parkinson’s disease（PD）,the most common movement disorder,alpha-synuclein is the major component in LB and the A53T missense mutation in alpha-synuclein causes an early onset automosomal dominant form of familial *** of intensive studies for the past decade,the physiology function of alpha-synuclein and its role in the pathogenesis of PD remain *** wild-type or mutant alpha-synuclein transgenic mouse models have been developed to model this type of *** none of them develop classic PD pathology,such as LB formation and nigrostriatal dopaminergic neuron ***,we decided to generate a novel conditional alpha-synuclein A53T mouse model using tetracycline gene regulation system,which allow us to spatially and temporally control the expression of mutant *** our initial experiment,we selectively expressed alpha-synuclein in the forebrain under the control of CamKII *** have achieved high level expression of the alpha-synuclein A53T mutant protein in the olfactory bulb,striatum,cerebral cortex,and *** interestingly,alpha-synuclein transgene displayed a mosaic expression pattern at substantia nigra in which～16%of nigrostriatal dopaminergic neurons expressed the mutant gene, alpha-synuclein aggregates and astrogliosis were found in mice at 2 months of *** prominent LB-like alphasynuclein aggregation was observed in 6-month old mice,which also showed a significant loss（＞30%） of mutant alphasynuclein -positive nigrostriatal dopaminergic neurons compared to 2-month old mice,reflecting a progressive dopaminergic neuron degeneration in this mouse *** summary,we have developed the first genetic mouse model for PD that displays typical PD-like *** will continue to work on this mouse model to define the cellular and molecular mechanisms underlying dopaminergic neuron degenerati

关键词： alpha-synuclein Parkinson’s disease(PD) nigrostriatal dopaminergic neuron Lewy Body mouse model tetracycline gene regulation system

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