| 研究課題/領域番号 |
17K18362
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| 研究機関 | 国立研究開発法人理化学研究所 |
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研究代表者 |
張 王其 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (20525604)
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| 研究期間 (年度) |
2017-04-01 – 2020-03-31
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| キーワード | PIGA / conditional knockout / development / epilepsy |
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| 研究実績の概要 |
We successfully deleted PIGA gene either in forebrain excitatory neurons or in inhibitory neurons by using the conditional knockout strategy. Since PIGA is an X chromosome linked gene, we could get deletion of PIGA in the entire specific cell population in male mouse, and we could get a deletion in half of the specific cell population due to x-inactivation in female mouse. (1)Deletion of PIGA in all inhibitory neurons resulted in developmental abnormality and embryo death.(2)Deletion of PIGA in all forebrain excitatory neurons resulted in embryo lethality. (3)Deletion of PIGA in all thalamus neurons didn't cause embryo death and the mutants could grow normally to adults. However, the susceptibility to kainic acid induced seizures was significantly increased in mutants.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
We observed much more striking phenotypes in the PIGA conditional knockout mice than what we previously expected. When PIGA was specifically deleted in the inhibitory neurons, the embryo stopped development on E7. When PIGA was deleted in forebrain excitatory neurons, the E13.5 embryo showed neural tube defects and anencephaly, and the embryo failed to continue to develop to birth. When PIGA was deleted in thalamus excitatory neurons, the mutants could develop normally to adults. Further analysis of the thalamus specific PIGA deletion mice revealed that kainic acid induced more severe seizure activity, both physically and behaviorally, on these mutants.
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| 今後の研究の推進方策 |
As planned, we will continue to assay the histological and physiological changes in our conditional mutated mice in more details. In addition, we will express the exogenous PIGA in our interested neural circuits by AAV virus injection, so that we can investigate the rescue effects of the gene therapy.
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| 次年度使用額が生じた理由 |
We will need to maintaining the conditional knockout mice; We will need to prepare EEG recording and silicon probe recording related items; We will need to prepare AAV virus packaging related items. We will need language editing for our publication of current project.
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