Investigation of A Child Disease with Epigenetic Disorder -Rett Syndrome-

一种伴有表观遗传障碍的儿童疾病 -Rett 综合征 - 的调查

• 批准号: 15390330
• 负责人: KUBOTA Takeo
• 金额: $ 9.41万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390330/
• 关键词: epigenetics; mental retardation; Rett syndrome; DNA methylation; MeCP2; neuronal cell; glial cell; phosphorylation; 小児疾患; ニューロン; シナプス; ノックアウトマウス; ノック

[Aim]Rett syndrome is an autistic disease caused by MeCP2 gene mutations. However, what happened in the brain is remained to be clarified. The aim of this project to know abnormalities in the brain cells when MeCP2 protein do not function well.[1st fiscal year]We identified that spine formation on dendrites of neurons in primary neuronal cells derived from the brain of MeCP2 knock-out mouse (together with other findings, the manuscript is in preparation).[2nd fiscal year]We identified that MeCP2 protein is expressed in not only in neurons but also in glial cells. We also found that MeCP2 malfunction results in growth retardation of glial cells, suggesting that microcephaly seen in Rett syndrome patients may be related to the growth retardation of glial cells during early development (Nagai et al., Dev Brain Res 2005).[3rd fiscal year]We identified that MeCP2 protein is expressed in not only in the nucleus but also cytosol of a neuronal cell, and that cytosolic MeCP2 is phosphorylated whereas nucleic MeCP2 is not, suggesting that transport of MeCP2 from cytosol may be associated with phosphorylation (Manuscript submitted).[Further experiment]The findings in this project will contribute to the understanding of pathogenesis of Rett syndrome and other autistic diseases.

[目的]Rett综合征是一种由MeCP2基因突变引起的自闭症。然而，大脑中发生了什么仍有待澄清。该项目的目的是了解当 MeCP2 蛋白不能正常发挥作用时脑细胞中的异常情况。[第一个财政年度]我们发现，来自 MeCP2 敲除小鼠大脑的原代神经元细胞中的神经元树突上形成了脊柱。与其他发现一起，手稿正在准备中）。[第二财年]我们发现MeCP2蛋白不仅在神经元中表达，也在神经胶质细胞中表达。我们还发现 MeCP2 功能障碍会导致神经胶质细胞生长迟缓，这表明雷特综合征患者中出现的小头畸形可能与早期发育过程中神经胶质细胞的生长迟缓有关（Nagai 等人，Dev Brain Res 2005）。 [第 3 财报[year]我们发现MeCP2蛋白不仅在神经元细胞的细胞核中表达，还在细胞质中表达，并且细胞质MeCP2被磷酸化，而核酸MeCP2则没有，表明MeCP2从细胞质中的转运可能与磷酸化有关（手稿已提交）。[进一步实验]该项目的研究结果将有助于了解Rett综合征和其他自闭症疾病的发病机制。

项目成果

Myelination state of a fetal case of Pelizaeus-Merzbacher disease : Immunopathological considerations.

Pelizaeus-Merzbacher 病胎儿病例的髓鞘形成状态：免疫病理学考虑。

• 发表时间: 2003
• 期刊: Annal Neurol 54
• 作者: Shiraishi K;Itoh M;Sano K;Takashima Y;Kubota T.
• 通讯作者: Kubota T.

Jo et al.: "Mutational Analysis of WASP Gene in Two Korean Families with Wiskott-Aldrich Syndrome."Int J Hematol. 78・1. 40-44 (2003)

Jo 等人：“两个患有 Wiskott-Aldrich 综合征的韩国家族的 WASP 基因突变分析”，《Int J Hematol》78・1（2003 年）。

Dilinoleoyl-phsphatidylethalamine from Hericium erinaceum protects against ER stress-dependent Neur2a cell death via protein kinase C pathway.

猴头菇中的二亚油酰磷脂酰乙胺通过蛋白激酶 C 途径防止 ER 应激依赖性 Neur2a 细胞死亡。

• 发表时间: 2006
• 期刊: J Nutr Biochem Epub ahead of print
• 作者: Nagai K;et al.
• 通讯作者: et al.

Severe Prader-Willi syndrome with a large deletion of chromosome 15 due to an unbalanced t(15;22)(q14;11.2) translocation.

由于不平衡 t(15;22)(q14;11.2) 易位导致 15 号染色体大量缺失的严重 Prader-Willi 综合征。

• 发表时间: 2003
• 期刊: Clinical Genet 63・1
• 作者: Nagai K;et al.;Matsumura et al.
• 通讯作者: Matsumura et al.

久保田健夫: "加齢・疾患とエピジェネティックス「神経疾患とエピジェネティックス」"現代医療. 35・5. 122-128 (2003)

久保田武夫：“衰老/疾病和表观遗传学‘神经疾病和表观遗传学’”现代医学35・5。