Authors: ZHIMIN XU, NOOR BAHADAR, YINGXIN ZHANG, SHUANG TAN, ZHONGZE WANG, BINGYI REN, SHITAO LIU, HUANYAN DAI, YAOWU ZHENG, BING HAN

Abstract: BEX family genes are expressed in various tissues and play significant roles in neuronal development. A mouse model of Bex3 gene knock-out was generated in this study, using the CRISPR-Cas9 system. Transcriptomic analysis of the brain was performed to identify genes and pathways under Bex3 regulation. Essential biological functions under the control of Bex3 related to brain development were identified. Ninety-five genes were differentially expressed under Bex3-/- regulation, with 53 down and 42 up. Among down-regulated genes, LOC102633156 is a member of zf-C2H2, Xlr3a is an X-linked lymphocyte regulated gene, LOC101056144 is a hippocampal related gene, 2210418O10Rik and Fam205a3 are cortex related genes. Among the upregulated genes, Zfp967 is a zf protein, Tgtp2 is a T cell-specific regulator, Trpc2 is a neuron-related gene, and Evi2 is related to NF1. A total of 34 KEGG disease terms were identified under the Bex3-/- regulation. The most prominent is non-syndromic X-linked mental retardation, where Fgd1 is enriched. Similarly, IRF, MBD, SAND, zf-BED, and zf-C2H2 were significantly enriched transcription factors. A further study is required to confirm and explain each aspect that has been identified in this study.

Keywords: CRISPR-Cas9, transgenic mouse model, transcriptome analysis, gene ontology analysis, KEGG pathway

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