Lab of Experimental Neurobiology, IRCCS National Neurological Institute C. Mondino, Via Mondino, 2, 27100, Pavia, Italy.
Neurotox Res. 2011 Aug;20(2):150-8. doi: 10.1007/s12640-010-9230-y. Epub 2010 Nov 17.
Flavin-containing monooxygenases (FMOs) are a family of microsomal enzymes involved in the oxygenation of a variety of nucleophilic heteroatom-containing xenobiotics. Recent results have pointed to a relation between Amyotrophic Lateral Sclerosis (ALS) and FMO genes. ALS is an adult-onset, progressive, and fatal neurodegenerative disease. We have compared FMO mRNA expression in the control mouse strain C57BL/6J and in a SOD1-mutated (G93A) ALS mouse model. Fmo expression was examined in total brain, and in subregions including cerebellum, cerebral hemisphere, brainstem, and spinal cord of control and SOD1-mutated mice. We have also considered expression in male and female mice because FMO regulation is gender-related. Real-Time TaqMan PCR was used for FMO expression analysis. Normalization was done using hypoxanthine-guanine phosphoribosyl transferase (Hprt) as a control housekeeping gene. Fmo genes, except Fmo3, were detectably expressed in the central nervous system of both control and ALS model mice. FMO expression was generally greater in the ALS mouse model than in control mice, with the highest increase in Fmo1 expression in spinal cord and brainstem. In addition, we showed greater Fmo expression in males than in female mice in the ALS model. The expression of Fmo1 mRNA correlated with Sod1 mRNA expression in pathologic brain areas. We hypothesize that alteration of FMO gene expression is a consequence of the pathological environment linked to oxidative stress related to mutated SOD1.
黄素单加氧酶（FMOs）是一类参与多种亲核杂原子含外源化学物氧化的微粒体酶。最近的研究结果表明，肌萎缩侧索硬化症（ALS）与 FMO 基因之间存在关联。ALS 是一种成年起病、进行性和致命的神经退行性疾病。我们比较了对照鼠种 C57BL/6J 和 SOD1 突变（G93A）ALS 小鼠模型中的 FMO mRNA 表达。在总脑以及小脑、大脑半球、脑干和脊髓等脑区中检测了 Fmo 的表达情况。我们还考虑了雌雄小鼠之间的表达差异，因为 FMO 的调控与性别有关。采用实时 TaqMan PCR 进行 FMO 表达分析。使用次黄嘌呤鸟嘌呤磷酸核糖转移酶（Hprt）作为管家基因进行归一化。除了 Fmo3 之外，Fmo 基因在对照和 ALS 模型小鼠的中枢神经系统中均可检测到表达。FMO 的表达在 ALS 小鼠模型中通常高于对照小鼠，Fmo1 在脊髓和脑干中的表达增加最为显著。此外，我们还发现 ALS 模型中雄性小鼠的 Fmo 表达高于雌性小鼠。Fmo1 mRNA 的表达与病理脑区中的 Sod1 mRNA 表达相关。我们假设 FMO 基因表达的改变是与突变的 SOD1 相关的氧化应激相关的病理环境的结果。
