| 研究課題/領域番号 |
17K18362
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| 研究機関 | 筑波大学 |
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研究代表者 |
張 王其 筑波大学, 人間系, 助教 (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 / GPI / epilepsy / dementia / ataxia / seizure / excitatory neuron / inhibitory neuron |
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| 研究実績の概要 |
PIGA is the first intermediate enzyme in the biosynthetic pathway of GPI anchor. In the clinic, PIGA mutation could cause intractable mental diseases. However,the underlying neurobiology is poorly understood. Here we successfully constructed conditional KO mice (specific ablation of PIGA in different brain regions). We found that lack of PIGA in inhibitory or forebrain excitatory neurons led to embryo death. Whereas the CKO mice lacking PIGA in thalamic neurons, became significant more susceptible to develop seizures.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
By combining Emx-Cre, Vgat-Cre and Pkcd-Cre mice with PIGA floxed mice, we successfully got conditional knockout mice with the ablation of PIGA specifically in inhibitory neurons,in forebrain excitatory neurons or in thalamus neurons. Since PIGA is a x-chromosome linked gene, we realized the full ablation of PIGA in the specific cell populations in male double positive mice and half-ablation of PIGA in female double positive mice. This special opportunity allowed to us to study the phenotypes of the conditional knout-out lines in a fine details, therefore comparing to our previous plan, we made more interesting discoveries.
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| 今後の研究の推進方策 |
Since I just moved to a new university, it took me a time to set up the experimental system. Next step, we would like to use neuralynx system and silicon probe to detect the in vivo electrophysiolgical changes of the conditional mouse lines. In addition, we would like to use AAV virus mediated PIGA gene expression in hippocampus and thalamus to study the region-specific gene rescue effects.
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| 次年度使用額が生じた理由 |
Due to my job change, I needed to move mice and equipment from my previous lab to current lab, and it took a time to start everything in a new place, therefore we have to postpone some budget usage and experiments to the next fiscal year.
Based on some new phenotype we observed in our mice, we will need to do more experiments to understand the mechanisms. In addition, we need to attend conference and publish our data.
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