2023 Fiscal Year Final Research Report
Mechanisms of low temperature tolerance common to mammals as a basis for induction of artificial hibernation.
| Project/Area Number |
22K19243
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 42:Veterinary medical science, animal science, and related fields
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| Research Institution | Gifu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
堀井 有希 岐阜大学, 糖鎖生命コア研究所, 助教 (20888531)
宮脇 慎吾 岐阜大学, 応用生物科学部, 准教授 (70756759)
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| Project Period (FY) |
2022-06-30 – 2024-03-31
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| Keywords | 冬眠 / 低体温 / 低温ショックタンパク質 / 転写後調節 / ゲノム編集 / 選択的スプライシング |
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| Outline of Final Research Achievements |
We have previously found that the expression of cold inducible RNA binding protein (CIRP) is regulated at the splicing level in hibernating animals. The present study examined whether this regulatory mechanism commonly functions in non-hibernating animals to avoid organ injury that occurs during hypothermia.
Two types of genome-edited mice were generated: hibernating type (exhibiting a hibernating splicing pattern) and variant type (without a hibernating pattern). When hypothermia was forcibly induced, severe arrhythmias appeared in the variant type when the body temperature decreased to less than 20°C, and cardiac arrest occurred in about half of them. In contrast, arrhythmias in the hibernating type were minor and only a few individuals experienced cardiac arrest. These findings indicate that expression of functional CIRP by hibernation-like splicing mechanism is effective in making the heart tolerant to low temperatures.
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| Free Research Field |
神経生理学
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| Academic Significance and Societal Importance of the Research Achievements |
人工冬眠は極めて困難な課題であるが、成功すれば医療に大きな変革をもたらすと期待できる。しかしながら、冬眠しない動物では25℃以下の低体温になると臓器が傷害されることが障壁となって、人工冬眠は実現していない。本研究では、低温下で細胞を保護する作用のあるCIRPに着目し、冬眠動物が示す特徴的は発現をゲノム編集技術によりマウスで再現した。このようなマウスでは体温が20℃以下になっても正常な心拍動が維持されることが明らかになったことは、冬眠しない動物に冬眠様低体温に誘導し、医療応用できる可能性を示唆するものであり、学術的意義、社会的意義の高い発見であると言える。
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