2007 Fiscal Year Final Research Report Summary
An investigation for transcriptional mechanisms of the autisim-sensitive gene, Neurorigiin 4
| Project/Area Number |
18590397
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
NAKAYAMA Atsuo Institute for Developmental Research, Aichi Human Service Center, Inst for Developmental Research, Dept Embryology, Dept Chief (50227964)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Eiko Inst for Developmental Research, Dept Embryology, Research Assistant (10393141)
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| Project Period (FY) |
2006 – 2007
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| Keywords | autism / sensitive gene / transcriptional regulation / epigenetics / expression / DNA methylation |
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| Research Abstract |
To elucidate the mechanisms regulating the expression of the autism-sensitive gene, Neuroligin(NLGN) 4, we first studied the expression pattern of its coding product, NLGN 4 protein. NLGN 4 was expressed exclusively in neurons, but not in glial cells in the brain. Some neurons, those in the supra-optic nucleus and the periventncular nucleus, express NLGN4 protein at the high level, while other neurons including. Purkinje cells scarcely express NLGN4.
Based on the above results, we analyzed regulatory region of the NLGN 4 gene. We identified that the NLGN 4 gene has multiple exon1s, i. e. exons 1A-1D, and the major transcripts expressed in neuronal cells seemed derived from exon 1A. Reporter assay indicated that 270bp 5' flanking region of exon 1A indeed has transcriptional activity, and the region is sufficient for neuronal cell-specific expression of the gene, since the fragment drove the reporter gene expression in a human neuroblastoma cell line, but not in a human epithelial cell ca
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rcinoma cell line. Further dissection of the region to elucidate the essential and cell type-specific elements is in progress. We analyzed the methylation status of the region in NLGN 4 expressing cells and not expressing cells, and tissues with and without NLGN 4 expression, as well. We identified 15 methylation-sensitive(CpG) sites within 410bp region surrounding the transcription start site of exon 1A. Eight among 15 CpG sites were heavily methylated in the epithelilal cell carcinoma cells, while they were not methylated in the neuroblastoma cells. Nine CpG sited in the genomic DNA prepared from a human liver were exclusively methylated. Those in the genomic DNA from human brains were mostly methylated, but they contained some DNA clones without methylation. Since the genomic DNA from the brain is heterogenous in terms of their cell type origins, DNA clones without methylation were supposed derived from neuron, while those with methylation were mostly from glial cells. Thus, these results suggested that the promoter region of the human NLGN 4 gene is under control of the epigenetic regulation. Less
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[Journal Article] Age-related changes in BDNF protein levels in human serum : differences between autism cases and normal controls2007
Author(s)
Ritsuko Katoh-Semba, Rie Wakakko, Taku Komori, Hiroko Shigemi, Noriko Miyazaki, Hironori Ito, Toshiyuki Kumagai, Masako Tsuzuki, Kenji Shigemi, Futoshi Yoshida, Atsuo Nakayama
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Journal Title
Int J Developmental Neurosci 25
Pages: 367-372
Description
「研究成果報告書概要(欧文)」より
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