Genetic functions for human encephalization with efficient technology to produce genetically humanized mice
| Project/Area Number |
16K18402
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Laboratory animal science
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| Research Institution | Osaka University (2017-2018)
National Institute of Genetics (2016) |
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Principal Investigator |
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| Research Collaborator |
Koide Tsuyoshi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | ゲノムヒト化 / マウス / ゲノム編集 / Cdk5rap2 / ゲノムヒト化マウス / 大脳化 / CRISPR/Cas9 / 遺伝子ヒト化モデル |
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| Outline of Final Research Achievements |
In this study, we established and analyzed several knockout and genetically humanized mice at both candidate gene and non-coding regions associated with human encephalization. The KO and SNP-humanized mice at Cdk5rap2 were established by genome editing technologies. Phenotyping analysis of the KO and KI mice revealed that the human-specific sequence of this gene can have an influence on the size of the body via feeding behavior. Second, we also established the genetically humanized mice at the non-coding region in chromosome 7 which was selected by comparative genomic analysis with primate and non-primate genome. The strain demonstrated the decline of birth rate.
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| Academic Significance and Societal Importance of the Research Achievements |
進化過程でヒトが獲得した高度な認知能力・言語能力は、神経細胞数の増加による大脳皮質の肥大化やしわ構造の獲得といった脳形態の変化（大脳化）により生じたと考えられている。こうした大脳化関連ゲノム領域の生体内における機能を明らかとするため、ゲノム編集技術を用いてヒト型にゲノム改変したマウスモデルを作成し、その表現型を解析した。本研究を通じて効率的なゲノムヒト化マウスの作製基盤を構築したとともに、進化で保存されてきたヒト特異的配列が発生や体重などの表現型に影響することを明らかにした。この結果はヒト大脳化や認知能力の高度化における遺伝的基盤の重要性を示している。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] CLICK: one-step generation of conditional knockout mice.2018
Author(s)
Miyasaka Y, Uno Y, Yoshimi K, Kunihiro Y, Yoshimura T, Tanaka T, Ishikubo H, Hiraoka Y, Takemoto N, Tanaka T, Ooguchi Y, Skehel P, Aida T, Takeda J, Mashimo T.
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Journal Title
BMC Genomics
Volume: 19
Pages: 000-000
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice.2017
Author(s)
Horii Y, Nagasawa T, Sakakibara H, Takahashi A, Tanave A, Matsumoto Y, Nagayama H, Yoshimi K, Yasuda MT, Shimoi K, Koide T.
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Journal Title
Scientific Reports
Volume: 7
Pages: 6991-6991
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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