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

• Material Type: 博士論文
• Title: Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model.
• Author/Editor: 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
• Author Heading: 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
• Publication, Distribution, etc.: National Academy of Sciences
• Publication Date: 2013-10-22
• Publication Date (W3CDTF): 2013-10-22
• Alternative Title: 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
• Periodical title: Proceedings of the National Academy of Sciences of the United States of America Vol. No. p.
• No. or year of volume/issue: 110 43
• Volume: 110
• Issue: 43
• Pages: 17552-17557
• ISSN (Periodical Title): ISSN : 0027-8424
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2014-03-17
• Dissertation Number: 乙第1331号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: hippocampus; dentate gyrus
• Target Audience: 一般
• Note (General): 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
• Source: fulltext; 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; 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; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2716/3/03%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1073/pnas.1312661110
• Periodical Title (NCID): AA10808769; https://ci.nii.ac.jp/ncid/AA10808769
• Data Provider (Database): 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
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU