Enhancer trap analysis for Autism Spectrum Disorder associated locus by utilizing Human BAC transgenic mouse methodology

2014 Fiscal Year Final Research Report

• Project/Area Number: 24510280
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical genome science
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: INOUE Yukiko 独立行政法人国立精神・神経医療研究センター, 神経研究所 疾病研究第六部, 流動研究員 (30611777)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 自閉症スペクトラム / SNP / ヒトBAC / BACトランスジェニックマウス / アンチセンスRNA / Moesin

Outline of Final Research Achievements

A recent genome-wide association study indicated a significant association of ASD with the SNPs, rs4307059 and five others, located in a gene-poor region between CDH10 and CDH9 on chromosome 5p14.1. In addition, the transcription of a novel noncoding RNA antisense to Moesin mRNA from this ASD risk SNP region was reported.
In the present study, we applied bacterial artificial chromosome (BAC) based transgenic mouse methodology to analyze the enhancer activities of this risk SNP region. By using BACs containing the human genome sequences around the SNPs, we revealed that the region harbored the neocortical area, striatum and cerebellum specific enhancers for the aforementioned antisense RNA. Considering the actin filament linking ability of Moesin at axonal growth cones, balancing machinery of Moesin protein expression at distinct brain regions that relate to clinical conditions might well explain the common features of ASD.

Free Research Field

ゲノム医科学、神経発生生物学