Role of NRROS in microglia and perivascular macrophages in the brain

Mice deficient in NRROS exhibit neurological phenotype similar to ALS. Our previous work showed that in phagocytes, NRROS regulates the degradation of Nox2, the enzymatic component of the NADPH oxidase that generates reactive oxygen species. NRROS is expressed in phagocytes, including macrophages, neutrophils and microglia but not neurons. Previous results on RNA-sequencing from WT and NRRO KO CD11b+ population (NGS601) identified perivascular macrophage (pvm)-like expression profile in NRROS KO cells. FACS data revealed a loss of microglia and concomitant gain of pvm-like cells in the brains of NRROS KO mice. To further these findings, we would like to directly compare gene expression between WT microglia (n = 3), WT pvm (n = 3) and NRROS KO pvm (n = 3).NRROS缺陷小鼠展现出与肌萎缩侧索硬化症（Amyotrophic Lateral Sclerosis, ALS）相似的神经表型。我们此前的研究证实，在吞噬细胞中，NRROS可调控Nox2的降解——Nox2是产生活性氧的烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶的酶促组分。NRROS在吞噬细胞中表达，涵盖巨噬细胞、中性粒细胞与小胶质细胞，但不在神经元中表达。针对野生型（Wild Type, WT）与NRROS敲除（Knock Out, KO）CD11b阳性细胞群（NGS601）的RNA测序（RNA-sequencing）结果已在NRROS KO细胞中鉴定出血管周围巨噬细胞（perivascular macrophage, PVM）样表达谱。荧光激活细胞分选术（Fluorescence-Activated Cell Sorting, FACS）数据显示，NRROS KO小鼠脑内出现小胶质细胞丢失，同时伴随PVM样细胞增多的现象。为进一步验证上述研究发现，我们拟直接比较野生型小胶质细胞（n = 3）、野生型PVM（n = 3）与NRROS KO PVM（n = 3）之间的基因表达差异。