2013 Fiscal Year Final Research Report
Molecular pathological mechanisms of the brain development disorder using the chromatin-remodeling molecule ATRX gene knockout mouse
| 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)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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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 |
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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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[Journal Article] Melatonin reverses the decreases in hippocampal protein serine/threonine kinases observed in an animal model of autism2014
Author(s)
Tian Y, Yabuki Y, Moriguchi S, Fukunaga K, Mao PJ, Hong LJ, Lu YM, Wang R, Ahmed MM, Liao MH, Huang JY, Zhang RT, Zhou TY, Long S, Han F
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Journal Title
J Pineal Res
Volume: 56(1)
Pages: 1-11
Peer Reviewed
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[Journal Article] Reduced expression of the ATRX gene, a chromatin-remodeling factor, causes hippocampal dysfunction in mice2011
Author(s)
Nogami T1, Beppu H, Tokoro T, Moriguchi S, Shioda N, Fukunaga K, Ohtsuka T, Ishii Y, Sasahara M, Shimada Y, Nishijo H, Li E, Kitajima I
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Journal Title
Hippocampus
Volume: 21(6)
Pages: 678-687
Peer Reviewed
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