INSERM U910, Faculté de Médecine de La Timone, 27 Boulevard Jean Moulin, F-13385 Marseille Cedex 05, France.
Behav Brain Res. 2011 Jan 1;216(1):313-20. doi: 10.1016/j.bbr.2010.08.011. Epub 2010 Aug 14.
The methyl-CpG binding protein 2 (Mecp2) gene encodes a nuclear transcriptional modulator highly expressed in post-mitotic neurons. Mutations of this gene cause a large spectrum of neurological disorders in humans. Several lines of mice harboring a constitutional deletion of Mecp2 are available. The use of these models is crucial to understand the basis of Mecp2-related pathologies. However, most of the studies performed using these lines focused on different postnatal time points. The aim of the present study was to provide a more complete description of the behavioral phenotype of the Mecp2(tm1.1Bird) mice. To this aim, we used a modified version of the SHIRPA protocol and a set of sensorimotor tests and respiratory metabolism measurements, in a longitudinal study of the Mecp2-null male mice (Mecp2(-/y)) from three weeks (weaning) to eight weeks of age. Our data document, for the first time, the sequential appearance of the in vivo deficits in this mouse line. The observed deficits initially concern major parameters (such as body weight), and are followed by involuntary and sensitive defects (reflexes). Subsequently, motor functions and respiratory metabolism are severally impaired. A detailed description of these gradual defects may help to identify their neuronal origin and to elaborate novel therapeutic strategies.
甲基化-CpG 结合蛋白 2（Mecp2）基因编码一种在有丝分裂后神经元中高度表达的核转录调节剂。该基因的突变会导致人类出现多种神经发育障碍。几种携带 Mecp2 结构缺失的小鼠模型已经问世。这些模型的使用对于理解 Mecp2 相关病理的基础至关重要。然而，使用这些模型进行的大多数研究都集中在不同的出生后时间点。本研究的目的是提供 Mecp2(tm1.1Bird) 小鼠行为表型的更完整描述。为此，我们使用改良版的 SHIRPA 方案以及一系列感觉运动测试和呼吸代谢测量，对 3 至 8 周龄的 Mecp2 缺失雄性小鼠（Mecp2(-/y)）进行了纵向研究。我们的数据首次记录了该小鼠系中体内缺陷的序贯出现。观察到的缺陷最初涉及主要参数（如体重），随后是不自主和敏感的缺陷（反射）。随后，运动功能和呼吸代谢分别受到损害。对这些逐渐出现的缺陷的详细描述可能有助于确定其神经元起源，并制定新的治疗策略。
