Pathogenesis of Lethal Aspiration Pneumonia in Mecp2-null Mouse Model for Rett Syndrome.
Pathogenesis of Lethal Aspiration Pneumonia in Mecp2-null Mouse Model for Rett Syndrome.
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DOI：
10.1038/s41598-017-12293-8
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发表时间：
2017-09-20
影响因子：
4.6
通讯作者：
Matsuishi T
中科院分区：
文献类型：
--
作者：
Kida H;Takahashi T;Nakamura Y;Kinoshita T;Hara M;Okamoto M;Okayama S;Nakamura K;Kosai KI;Taniwaki T;Yamashita Y;Matsuishi T
Rett综合征（RTT）是一种神经发育障碍，主要由位于X染色体上的编码转录调节因子甲基-CpG结合蛋白2（MeCP 2）的基因突变引起。许多RTT患者有呼吸异常，如呼吸暂停和呼吸不规则，呼吸道感染是这些人最常见的死亡原因。先前的研究表明MeCP 2在肺中高度表达，但其在肺功能中的作用尚不清楚。在这项研究中，我们发现MeCP 2缺乏影响肺基因表达和结构。我们还发现，Mecp 2基因缺失的小鼠，也有呼吸问题，往往表现出炎症性肺损伤。这些损伤发生在肺叶的特定部位。此外，在Mecp 2基因敲除小鼠的受损肺中发现了可极化的异物。这些结果表明，误吸可能是Mecp 2基因敲除小鼠炎性肺损伤的原因之一。另一方面，MeCP 2缺乏影响了下脑干中几种神经调质基因的表达。其中，神经肽P物质（SP）的免疫染色在Mecp 2无效脑干减少。提示脑干SP表达的改变可能与自主神经功能失调有关，也可能是Mecp 2基因敲除小鼠误吸的原因之一。
Rett syndrome (RTT) is a neurodevelopmental disorder mainly caused by mutations in the gene encoding the transcriptional regulator Methyl-CpG-binding protein 2 (MeCP2), located on the X chromosome. Many RTT patients have breathing abnormalities, such as apnea and breathing irregularity, and respiratory infection is the most common cause of death in these individuals. Previous studies showed that MeCP2 is highly expressed in the lung, but its role in pulmonary function remains unknown. In this study, we found that MeCP2 deficiency affects pulmonary gene expression and structures. We also found that Mecp2-null mice, which also have breathing problems, often exhibit inflammatory lung injury. These injuries occurred in specific sites in the lung lobes. In addition, polarizable foreign materials were identified in the injured lungs of Mecp2-null mice. These results indicated that aspiration might be a cause of inflammatory lung injury in Mecp2-null mice. On the other hand, MeCP2 deficiency affected the expression of several neuromodulator genes in the lower brainstem. Among them, neuropeptide substance P (SP) immunostaining was reduced in Mecp2-null brainstem. These findings suggest that alteration of SP expression in brainstem may be involved in autonomic dysregulation, and may be one of the causes of aspiration in Mecp2-null mice.
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