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

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;開始ページ : 17552;終了ページ : 17557;PubMed番号 : http://www.ncbi.nlm.nih.gov/pubmed/24101523

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この本の情報

書名 Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model.
著作者等 National Academy of Sciences
Hiyama Hideki
Horiuchi Yasue
Illingworth Elizabeth
Iwamoto Takashi
JSTOR (Organization)
Keni Ni
Kimoto Sohei
Kishimoto Toshifumi
Landek-Salgado Melissa A
Muraki Kazue
Sawa Akira
Tajinda Katsunori
Tanigaki Kenji
Yamamoto Norio
Yoshida Atsuhiro
Toritsuka Michihiro
書名別名 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
出版元 National Academy of Sciences
刊行年月 1915-1979
ページ数 76 v.
大きさ 25-28 cm
ISSN 00278424
NCID AA11627282
AA00786025
AA10808769
AA12104563
※クリックでCiNii Booksを表示
言語 英語
出版国 アメリカ合衆国
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