CRISPR Cas9 Mediated Generation of Bex2 KO Mouse Model and Transcriptome Analysis of the Brain

Background. BEX family genes are expressed in many tissues and play significant roles in neuronal development. Methods. In this study, a mouse model of Bex2 gene knockout was generated, using the CRISPR-Cas9 system. A fragment of the coding exon was successfully deleted. RT-qPCR confirmed loss of gene expression at the mRNA level. A transcriptomic study of the brain was performed to identify genes and pathways under Bex2 regulation. Essential biological functions under the control of Bex2 related to brain development were identified. Results. A total of 93 genes were found as differentially expressed. Among up-regulated genes, Zfp967 and Zfp984, are zf protein-related genes. Tmsb15l is related to neuronal physiology. Among KEGG pathways, cell adhesion molecules (CAMs) and neuroactive ligand-receptor integration were most enriched. GO analysis identified cellular process, biological regulation, the metabolic process for Biological Processes. Cell, cell membrane, extracellular region and synapsis were found for Cellular Component. While binding, catalytic activity, molecular function were found for Molecular Function. A total of 53 KEGG disease terms were identified, included TNDM, Non-syndromic X-linked mental retardation, Neurodegeneration due to cerebral folate transport deficiency, Schizencephaly. Besides, HMGA, TF-Otx, RXR-like, SAND, zf-C2H2 and Homeobox transcription factors were enriched. A further study is required to confirm and explain each aspect identified.