Neurological defects in CAIX knockout mice

To further identify transcriptomic responses to CAIX deficiency in the brain, genome-wide cDNA microarray analyses were performed. Thirty-one and 37 genes were up- and down-regulated in the brain of Car9-/- mice as compared to wild-type mice. Functional annotation revealed that genes with increased expression are mainly involved in alternative splicing, nucleotide binding, RNA binding, and regulation of cellular protein metabolic process; whereas genes with reduced expression are chiefly implicated in cellular cation homeostasis, positive regulation of ion transport, Ubl conjugation, phosphorus metabolic process, and regulation of cell proliferation. Notably, the biological processes behaviour and locomotory behaviour are two prominent over-representation terms among the down-regulated genes, which is consistent with the results obtained from behavioural tests. Brain tissue samples were collected from five wild-type and four CAIX KO mice, respectively, at the age of eight months. Total RNAs were purified and used for cDNA microarray.为进一步探究脑中碳酸酐酶IX（CAIX）缺失所引发的转录组应答反应，本研究开展了全基因组cDNA微阵列分析。与野生型小鼠相比，Car9基因敲除（Car9-/-）小鼠的脑组织中分别有31个基因上调表达、37个基因下调表达。功能注释结果显示，上调表达的基因主要参与可变剪接、核苷酸结合、RNA结合以及细胞蛋白质代谢过程的调控；而下调表达的基因则主要参与细胞阳离子稳态、离子转运的正调控、泛素样（Ubl）缀合反应、磷代谢过程以及细胞增殖的调控。值得注意的是，在下调基因中，行为与运动行为这两个生物学过程条目显著富集，这与行为学实验所得结果一致。本研究分别于8月龄时采集了5只野生型小鼠与4只CAIX敲除（CAIX KO）小鼠的脑组织样本，提取总RNA后用于cDNA微阵列实验。