Separate respiratory phenotypes in methyl-CpG-binding protein 2 (Mecp2) deficient mice
Separate respiratory phenotypes in methyl-CpG-binding protein 2 (Mecp2) deficient mice
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DOI：
10.1203/01.pdr.0000203157.31924.4a
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发表时间：
2006-04-01
影响因子：
3.6
通讯作者：
Knopp, SJ
中科院分区：
文献类型：
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作者：
Bissonnete, JM;Knopp, SJ
Rett 综合征 (RTT) 是一种由 X 连锁基因甲基 CpG 结合蛋白 2 (MECP2) 突变引起的神经发育障碍，MECP2 编码 DNA 结合蛋白，该蛋白参与基因沉默。小鼠有丝分裂后神经元中 Mecp2 的选择性缺失会导致 Rett 样表型，其特征是运动活动和体重紊乱，表明这些症状完全是由神经元缺陷引起的。 RTT 表型包括过度换气后呼吸抑制的发作。在这里，我们表明呼吸表型取决于 Mecp2 缺陷的器官分布。 Mecp2 无效突变 (Mecp2(+/-)) 杂合雌性小鼠和神经元中蛋白质选择性缺失 (Mecp(2+/nestin-Crc lox)) 的雌性小鼠均表现出超过野生型 (WT) 的缺氧初始反应。然而，仅在 Mecp2(+/-) 动物中观察到缺氧过度换气后明显的呼吸抑制。在缺氧环境中添加二氧化碳可以消除呼吸抑制。 Mecp2(+/-) 的潮气量和肺容量较大，呼吸抑制与潮气量直接相关。总而言之，这些结果表明抑郁症是由于低碳酸血症引起的。在这个雷特综合征小鼠模型中，呼吸抑制在 Mecp2 普遍缺乏的情况下可见，但当它仅限于神经元时则不然。
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations ill the X-linked gene methyl-CpG-binding protein 2 (MECP2) that encodes a DNA binding, protein involved in gene silencing. Selective deletion of Mecp2 in post-mitotic neurons in mice results in a Rett-like phenotype characterized by disturbances in motor activity and body weight, suggesting that these symptoms are exclusively Caused by neuronal deficiency. Included ill the RTT phenotype are episodes of respiratory depression that follow hyperventilation. Here we show that the respiratory phenotype depends on the organ distribution of Mecp2 deficiency. Both female mice heterozygous for a null mutation in Mecp2 (Mecp2(+/-)) and those with selective deletion of the protein in neurons (Mecp(2+/nestin-Crc lox)), showed an initial response to hypoxia that exceeded that in wild type (WT). However, marked respiratory depression following hypoxic hyperventilation was only seen in Mecp2(+/-) animals. Addition of carbon dioxide to the hypoxic exposure eliminated the respiratory depression. Tidal Volume and lung Volume were larger in Mecp2(+/-) and respiratory depression was directly related to tidal volume. Taken together these results indicate that the depression is due to hypocapnia. Respiratory depression in this Mouse model of Rett Syndrome is seen in with ubiquitous deficiency in Mecp2 but not when it is confined to neurons.