Barbato Eric, Mianzo Hannah, Litman Paul, Darrah Rebecca
Case Western Reserve University, US.
Cincinnati Children's Hospital Medical Center, US.
J Circadian Rhythms. 2019 Apr 18;17:2. doi: 10.5334/jcr.175.
Cystic fibrosis (CF) is autosomal recessive disease that affects multiple body systems. CF patients often experience sleep disturbances, altered sleep patterns, and sleep apnea. Sleep in mammals is controlled in part by circadian clock genes, including and . The purpose of this study was to gain a better understanding of the biological underpinnings of disordered sleep experienced in CF. To accomplish this, we evaluated circadian clock gene expression profiles in CF and wildtype mice, divided into two subgroups each based on sleep condition. One subgroup of each genotype was permitted to maintain their sleep-wake cycle while the other was deprived of sleep for six hours prior to sacrifice. Brain, skeletal muscle, jejunum, colon, lung and adipose tissues were collected from each mouse. Quantitative polymerase chain reaction (PCR) was used to quantify expression of and and expression levels were compared between study groups. Our comparisons showed distinct differences between the CF groups and the wildtype groups under both sleep conditions. Additionally, we found the CF mice that had been sleep deprived had severely dysregulated expression of all measured genes in the lung apart from . Our findings suggest that (1) disordered sleep in CF may be caused by circadian system dysregulation and (2) the loss of the cystic fibrosis transmembrane conductance regulator (CFTR) is a causative factor in the dysregulated circadian clock gene expression profiles of CF mice.
囊性纤维化（CF）是一种常染色体隐性疾病，会影响多个身体系统。CF患者经常出现睡眠障碍、睡眠模式改变和睡眠呼吸暂停。哺乳动物的睡眠部分受生物钟基因控制，包括……和……。本研究的目的是更好地了解CF患者出现的睡眠紊乱的生物学基础。为实现这一目标，我们评估了CF小鼠和野生型小鼠的生物钟基因表达谱，每种小鼠根据睡眠状况分为两个亚组。每种基因型的一个亚组被允许维持其睡眠-觉醒周期，而另一个亚组在处死前被剥夺睡眠6小时。从每只小鼠收集脑、骨骼肌、空肠、结肠、肺和脂肪组织。使用定量聚合酶链反应（PCR）来量化……和……的表达，并比较研究组之间的表达水平。我们的比较显示，在两种睡眠条件下，CF组和野生型组之间存在明显差异。此外，我们发现，被剥夺睡眠的CF小鼠，除了……之外，肺中所有检测基因的表达均严重失调。我们的研究结果表明：（1）CF患者的睡眠紊乱可能是由昼夜节律系统失调引起的；（2）囊性纤维化跨膜传导调节因子（CFTR）的缺失是CF小鼠生物钟基因表达谱失调的一个致病因素。
