Identification of genes associated with cortical malformation using a transposon-mediated somatic mutagenesis screen in mice

I. Ling Lu, Chien Chen, Chien Yi Tung, Hsin Hung Chen, Jia Ping Pan, Chia Hsiang Chang, Jia Shing Cheng, Yi An Chen, Chun Hung Wang, Chia Wei Huang, Yi Ning Kang, Hsin Yun Chang, Lei Li Li, Kai Ping Chang, Yang Hsin Shih, Chi Hung Lin, Shang Yeong Kwan, Jin Wu Tsai*

*此作品的通信作者

研究成果: Article同行評審

19 引文 斯高帕斯(Scopus)

摘要

Mutations in genes involved in the production, migration, or differentiation of cortical neurons often lead to malformations of cortical development (MCDs). However, many genetic mutations involved in MCD pathogenesis remain unidentified. Here we developed a genetic screening paradigm based on transposon-mediated somatic mutagenesis by in utero electroporation and the inability of mutant neuronal precursors to migrate to the cortex and identified 33 candidate MCD genes. Consistent with the screen, several genes have already been implicated in neural development and disorders. Functional disruption of the candidate genes by RNAi or CRISPR/Cas9 causes altered neuronal distributions that resemble human cortical dysplasia. To verify potential clinical relevance of these candidate genes, we analyzed somatic mutations in brain tissue from patients with focal cortical dysplasia and found that mutations are enriched in these candidate genes. These results demonstrate that this approach is able to identify potential mouse genes involved in cortical development and MCD pathogenesis.

原文English
文章編號2498
期刊Nature Communications
9
發行號1
DOIs
出版狀態Published - 1 12月 2018

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