| Project/Area Number |
16K15233
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
新藤 隆行 信州大学, 学術研究院医学系, 教授 (90345215)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ゲノム編集 / 発生工学 / CRISPR/Cas9 / 遺伝子改変マウス / 疾患モデル動物 / 母性Cas9 / アドレノメデュリン / 多因子性疾患 / 高血圧 / アトドレノメデュリン / CRISPR / RAMP / 母性RNA / Cas9 |
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| Outline of Final Research Achievements |
We have developed a new strategy; maternal Cas9-based genome editing system. This system can confer simultaneous genome editing in multiple target loci when the guide (g)RNAs only were introduced into murine zygotes from transgenic mice overexpressing Cas9 systemically. First, we demonstrated that the system had high frequencies of insertion/deletion mutations and knock-in of a target sequence and was associated with low-level mosaicism. Furthermore, the birth rate increased significantly when compared with that obtained from zygotes in the presence of exogenous Cas9 protein (or mRNA) + gRNAs. The rate for simultaneous multi-gene-edited pups produced was markedly higher than that produced through zygote with exogenous Cas9 protein + 10 kinds of gRNAs. Then, using this system, we have produced simultaneously the model mice with 1~5 modified genes which are candidate for polygenic/multifactor diseases associated with hypertension, and observed in them with high or low blood pressure.
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