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• W2065329118 abstract "Certain inherited progressive neurodegenerative disorders, such as spinocerebellar ataxia (SCA), affect neurons in large areas of the central nervous system (CNS). The selective expression of disease-causing and therapeutic genes in susceptible regions and cell types is critical for the generation of animal models and development of gene therapies for these diseases. Previous studies have demonstrated the advantages of the short synapsin I (SynI) promoter (0.5 kb) as a neuron-specific promoter for robust transgene expression. However, the short SynI promoter has also shown some promoter activity in glia and a lack of transgene expression in significant areas of the CNS. New methods: To improve the SynI promoter, we used a SynI promoter that is twice as long (1.0 kb) as the short SynI promoter and incorporated a minimal CMV (minCMV) sequence. We observed that the 1.0 kb rat SynI promoter with minCMV [rSynI(1.0)-minCMV] exhibited robust promoter strength, excellent neuronal specificity and wide-ranging transgene expression throughout the CNS. Comparison with existing methods: Compared with the two previously reported short (0.5 kb) promoters, the new promoter was superior with respect to neuronal specificity and more efficiently transduced neurons. Moreover, transgenic mice expressing the mutant protein ATXN1[Q98], which causes SCA type 1 (SCA1), under the control of the rSynI(1.0)-minCMV promoter showed robust transgene expression specifically in neurons throughout the CNS and exhibited progressive ataxia. rSynI(1.0)-minCMV drives robust and neuron-specific transgene expression throughout the CNS and is therefore useful for viral vector-mediated neuron-specific gene delivery and generation of neuron-specific transgenic animals." @default.
• W2065329118 created "2016-06-24" @default.
• W2065329118 creator A5001341469 @default.
• W2065329118 creator A5023936492 @default.
• W2065329118 creator A5073680568 @default.
• W2065329118 date "2014-02-01" @default.
• W2065329118 modified "2023-09-26" @default.
• W2065329118 title "Generation of a neurodegenerative disease mouse model using lentiviral vectors carrying an enhanced synapsin I promoter" @default.
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• W2065329118 doi "https://doi.org/10.1016/j.jneumeth.2013.12.004" @default.
• W2065329118 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24361760" @default.
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