Effect of knockout of and pathogenic mutations in Hnrnph2 on gene expression in mouse cortex

To investigate the effect of knockout of and pathogenic mutatations in Hnrnph2, we generated mouse lines in which endogenous Hnrnph2 has been knocked out, or 2 pathogenic mutations (R206W, P209L) have been knocked into the endogenous Hnrnph2 using CRISPR Cas-9. We then performed gene expression profiling analysis using data obtained from RNA-seq of bulk cortex from male mice aged 8 weeks (knockout and R206W knockin lines) or 3 weeks (P209L knockin line) and age matched littermate controls (n=3 per grpup).为探究Hnrnph2基因敲除及其致病突变的生物学效应，我们利用CRISPR-Cas9基因编辑技术构建了三类小鼠品系：一类为内源性Hnrnph2基因敲除小鼠，另外两类为通过将两种致病突变（R206W、P209L）定点敲入内源Hnrnph2基因所获得的敲入小鼠。随后，我们针对不同品系雄性小鼠的全皮层组织开展RNA测序（RNA-seq），并基于所得数据进行基因表达谱分析：其中8周龄小鼠涵盖基因敲除组与R206W敲入组，3周龄小鼠为P209L敲入组，同时设置年龄匹配的同窝野生型对照小鼠，每组各3只。