ナカムラ カエ   NAKAMURA KAE
  中村 加枝
   所属   関西医科大学  生理学講座
   職種   教授
論文種別 原著(症例報告除く)
言語種別 英語
査読の有無 査読あり
表題 Identification of neuron-type specific promoters in monkey genome and their functional validation in mice.
掲載誌名 正式名:Biochemical and biophysical research communications
略  称:Biochem Biophys Res Commun
ISSNコード:0006291X/10902104
掲載区分国外
巻・号・頁 518(4),pp.614-624
著者・共著者 Nagai Y, Nishitani N, Yasuda M, Ueda Y, Fukui Y, Andoh C, Shirakawa H,
Nakagawa T, Inoue KI, Nagayasu K, Kasparov S, Nakamura K, Kaneko S.
発行年月 2019/10
概要 Viral gene delivery is one of the most versatile techniques for elucidating the mechanisms underlying brain dysfunction, such as neuropsychiatric disorders. Due to the complexity of the brain, expression of genetic tools, such as channelrhodopsin and calcium sensors, often has to be restricted to a specified cell type within a circuit implicated in these disorders. Only a handful of promoters targeting neuronal subtypes are currently used for viral gene delivery. Here, we isolated conserved promoter regions of several subtype-specific genes from the macaque genome and investigated their functionality in the mouse brain when used within lentiviral vectors (LVVs). Immunohistochemical analysis revealed that transgene expression induced by the promoter sequences for somatostatin (SST), cholecystokinin (CCK), parvalbumin (PV), serotonin transporter (SERT), vesicular acetylcholine transporter (vAChT), substance P (SP) and proenkephalin (PENK) was largely colocalized with specific markers for the targeted neuronal populations. Moreover, by combining these results with in silico predictions of transcription factor binding to the isolated sequences, we identified transcription factors possibly underlying cell-type specificity. These findings lay a foundation for the expansion of the current toolbox of promoters suitable for elucidating these neuronal phenotypes.
DOI 10.1016/j.bbrc.2019.08.101.
PMID 31451217