| Project/Area Number |
23300147
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Fusional basic brain science
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| Research Institution | University of Toyama |
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Principal Investigator |
KITAJIMA Isao 富山大学, 大学院医学薬学研究部(医学), 教授 (50214797)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Hisashi 富山大学, 大学院・医学薬学研究部(医学), 教授 (00239617)
FUKUNAGA Kohji 東北大学, 薬学研究科(研究員), 教授 (90136721)
別府 秀幸 富山大学, 大学院医学薬学研究部(医学), 准教授 (20550479)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | 脳発達障害 / エピジェネテイクス / クロマチンリモデリング / ノックアウトマウス / スパイン / 神経科学 / 脳神経疾患 / 応用動物 / 精神遅滞 / ＡＴＲ-Ｘ症候群 / コンデショナルノックアウトマウス / ＥＳ細胞 / 精神運動発達障害 / クロマチンロモデリング / ATRX症候群 / ES細胞 / 発達障害 |
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| Research Abstract |
Mutation in a chromatin remodeling protein, ATRX causes alfa-thalassemia X-linked mental retardation syndrome. We generated ATRX mutant mice lacking exon2 (ATRXdE2 mice). In a contextual fear conditioning test, total freezing time was decreased in ATRXdE2 mice. ATRXdE2 mice showed significantly reduced long-term potentiation (LTP) in the hippocampal CA1 region evoked by high-frequency stimulation. ATRXdE2 mice exhibited abnormal dendritic spine formation in the medial prefrontal cortex. We confirmed that increased phosphorylation of CaMKII,PAKs and reduced activity of protein phosphatase I. Next, we conditionally inactivated the homolog in mice, Atrx. Strategy for targeted deletion of exon 6. The PGK-neo selection cassette was inserted in intron 6 and the lox P target sites of the Cre recombinase were in intron 7. Cre-mediated ablation of full-length atrx protein in ES cells were established and then chimera ATRX loxp mice were developed.
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