Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model.

• 資料種別: 博士論文
• タイトル: Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model.
• 著者・編者: Toritsuka, Michihiro; Kimoto, Sohei; Muraki, Kazue; Landek-Salgado, Melissa A; Yoshida, Atsuhiro; Yamamoto, Norio; Horiuchi, Yasue; Hiyama, Hideki; Tajinda, Katsunori; Keni, Ni; Illingworth, Elizabeth; Iwamoto, Takashi; Kishimoto, Toshifumi; Sawa, Akira; Tanigaki, Kenji
• 著者標目: Toritsuka, Michihiro; Kimoto, Sohei; Muraki, Kazue; Landek-Salgado, Melissa A; Yoshida, Atsuhiro; Yamamoto, Norio; Horiuchi, Yasue; Hiyama, Hideki; Tajinda, Katsunori; Keni, Ni; Illingworth, Elizabeth; Iwamoto, Takashi; Kishimoto, Toshifumi; Sawa, Akira; Tanigaki, Kenji
• 出版事項: National Academy of Sciences
• 出版年月日等: 2013-10-22
• 出版年（W3CDTF）: 2013-10-22
• 並列タイトル等: 22q11欠失症候群モデルマウスの神経発達障害には、マイクロRNAが介在するCxcr4/Cxcl12シグナリングの欠損が寄与する
• タイトル（掲載誌）: Proceedings of the National Academy of Sciences of the United States of America Vol. No. p.
• 巻号年月日等（掲載誌）: 110 43
• 掲載巻: 110
• 掲載号: 43
• 掲載ページ: 17552-17557
• ISSN（掲載誌）: ISSN : 0027-8424
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2014-03-17
• 報告番号: 乙第1331号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: hippocampus; dentate gyrus
• 対象利用者: 一般
• 一般注記: type:Thesis; 22q11 deletion syndrome (22q11DS) frequently accompanies psychiatric conditions, some of which are classified as schizophrenia and bipolar disorder in the current diagnostic categorization. However, it remains elusive how the chromosomal microdeletion leads to the mental manifestation at the mechanistic level. Here we show that a 22q11DS mouse model with a deletion of 18 orthologous genes of human 22q11 (Df1/+ mice) has deficits in migration of cortical interneurons and hippocampal dentate precursor cells. Furthermore, Df1/+ mice show functional defects in Chemokine receptor 4/Chemokine ligand 12 (Cxcr4/Cxcl12; Sdf1) signaling, which reportedly underlie interneuron migration. Notably, the defects in interneuron progenitors are rescued by ectopic expression of Dgcr8, one of the genes in 22q11 microdeletion. Furthermore, heterozygous knockout mice for Dgcr8 show similar neurodevelopmental abnormalities as Df1/+ mice. Thus, Dgcr8-mediated regulation of microRNA is likely to underlie Cxcr4/Cxcl12 signaling and associated neurodevelopmental defects. Finally, we observe that expression of CXCL12 is decreased in olfactory neurons from sporadic cases with schizophrenia compared with normal controls. Given the increased risk of 22q11DS in schizophrenia that frequently shows interneuron abnormalities, the overall study suggests that CXCR4/CXCL12 signaling may represent a common downstream mediator in the pathophysiology of schizophrenia and related mental conditions.; 博士（医学）・乙1331号・平成26年3月17日; identifier:Proceedings of the National Academy of Sciences of the United States of America Vol.110 No.43 p.17552-17557; identifier:00278424; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2716; identifier:Proceedings of the National Academy of Sciences of the United States of America Vol. No. p., 110(43): 17552-17557
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.1073/pnas.1312661110
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

目次

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2716/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2716/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2716/3/03%e6%9c%ac%e6%96%87.pdf fulltext