Identification of neuron-type specific promoters in monkey genome and their functional validation in mice

Yuma Nagai, Naoya Nishitani, Masaharu Yasuda, Yasumasa Ueda, Yuto Fukui, Chihiro Andoh, Hisashi Shirakawa, Takayuki Nakagawa, Ken-ichi Inoue, Kazuki Nagayasu*, Sergey Kasparov, Kae Nakamura, Shuji Kaneko

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)
52 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)619-624
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume518
Issue number4
Early online date23 Aug 2019
DOIs
Publication statusPublished - 22 Oct 2019

Keywords

  • Inhibitory neuron
  • Monoamine
  • Promoter
  • Striatum
  • Viralvector

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