Identification of novel pain related factor based on transcriptome analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16480
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Nara Medical University
• Principal Investigator: Isonishi Ayami 奈良県立医科大学, 医学部, 助教 (10836018)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 疼痛 / 順遺伝学スクリーニング

Outline of Final Research Achievements

The mechanisms of pain generation and its transmission in the nervous system are diverse, and the full picture is not yet clear. In this study, we sought to identify the SNX25 gene responsible for pain by sequential genetic analysis of TG mice, which exhibit an extreme pain blunting phenotype, and to further elucidate its function. SNX25 KO mice exhibited a insensitive phenotype in response to mechanical and chemical stimuli at 2 months of age. Although thermal nociception in the Snx25 +/- mice was not affected at 2 months of age, older mice of 6-8 months displayed a higher latency to respond to a heat stimulus. Our findings suggest that there are time-specific differences in the mechanisms of pain generation to mechanical, chemical, and thermal stimuli, and that SNX25 and its downstream factors are involved as their regulators.

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

痛覚神経機能に関わる遺伝子を効率的に探索することは容易ではなく、その大規模な探索もこれまであまり行われてきていない。本研究は疼痛鈍麻TGマウスを用いて次世代シークエンスおよびcDNAマイクロアレイにより網羅的解析を行い、疼痛原因遺伝子の候補を見出した。現在の一般的な遺伝子の機能解析手法としては、ノックアウトなど遺伝子を操作してその表現型を調べる逆遺伝学が主要な方法であるが、本研究で用いた手法は、既に見えているTGマウスの表現型からその原因となる遺伝子を探りあてる順遺伝学であり、これまで機能が十分に知られていなかったSNX25の疼痛発生への関与を明らかにした点で学術的意義を有する。