The INO80E at 16p11.2 locus increases risk of schizophrenia in humans and induces schizophrenia-like phenotypes in mice

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	The INO80E at 16p11.2 locus increases risk of schizophrenia in humans and induces schizophrenia-like phenotypes in mice
	Hu, B; Yin, MY; Zhang, CY; Shi, Z; Wang, L; Lei, XM; Li, M; Li, SW; Tuo, QH
	2025
发表期刊	EBIOMEDICINE
ISSN	2352-3964
卷号	114
摘要	Background Chromosome 16p11.2 is one of the most significant loci in the genome-wide association studies (GWAS) of schizophrenia. Despite several integrative analyses and functional genomics studies having been carried out to identify possible risk genes, their impacts in the pathogenesis of schizophrenia remain to be fully characterized. Methods We performed expression quantitative trait loci (eQTL) and summary-data-based Mendelian randomization (SMR) analyses to identify schizophrenia risk genes in the 16p11.2 GWAS locus. We constructed a murine model with dysregulated expression of risk gene in the medial prefrontal cortex (mPFC) using stereotaxic injection of adeno-associated virus (AAV), followed by behavioural assessments, dendritic spine analyses and RNA sequencing. Findings We identified significant associations between elevated INO80E mRNA expression in the frontal cortex and risk of schizophrenia. The mice overexpressing Ino80e in mPFC (Ino80e-OE) exhibited schizophrenia-like behaviours, including increased anxiety behaviour, anhedonia, and impaired prepulse inhibition (PPI) when compared with control group. The neuronal sparse labelling assay showed that the density of stubby spines in the pyramidal neurons of mPFC was significantly increased in Ino80e-OE mice compared with control mice. Transcriptomic analysis in the mPFC revealed significant alterations in the mRNA levels of schizophrenia-related genes and processes related to synapses upon overexpressing Ino80e. Interpretation Our results suggest that upregulation of the Ino80e gene in mPFC may induce schizophrenia-like behaviours in mice, further supporting the hypothesis that INO80E is an authentic risk gene.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14512
专题	科研部门_转化基因组（李明）
推荐引用方式 GB/T 7714	Hu, B,Yin, MY,Zhang, CY,et al. The INO80E at 16p11.2 locus increases risk of schizophrenia in humans and induces schizophrenia-like phenotypes in mice[J]. EBIOMEDICINE,2025,114.
APA	Hu, B.,Yin, MY.,Zhang, CY.,Shi, Z.,Wang, L.,...&Tuo, QH.(2025).The INO80E at 16p11.2 locus increases risk of schizophrenia in humans and induces schizophrenia-like phenotypes in mice.EBIOMEDICINE,114.
MLA	Hu, B,et al."The INO80E at 16p11.2 locus increases risk of schizophrenia in humans and induces schizophrenia-like phenotypes in mice".EBIOMEDICINE 114(2025).

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