Dura Emmanuelle, Villard Laurent, Roux Jean-Christophe
INSERM, U910, Faculté de Médecine de La Timone, 27 Bd Jean-Moulin, Marseille, F-13385, France.
Brain Res. 2008 Oct 21;1236:176-84. doi: 10.1016/j.brainres.2008.08.021. Epub 2008 Aug 16.
Methyl CpG binding protein 2 (MeCP2) is a member of the methylated DNA binding protein family able to modulate the transcription of target genes. Mutations in MECP2 lead to a wide range of neurological phenotypes and the better known of these diseases is Rett Syndrome. All patients having a mutation in MECP2 are mentally retarded and most of them exhibit dysfunctions in autonomic processes that are controlled by the brainstem. Previous studies have shown that Mecp2 is developmentally and spatially regulated throughout the rodent brain but none of them investigated the brainstem. In the present study, we have quantified the levels of expression of the Mecp2 mRNA by real time PCR and MeCP2 protein by immunoquantifications, in different areas of the mouse brainstem during the postnatal development (P0, P7, P21, P35 and P55). We focused on regions of the pons and the medulla oblongata directly involved in the regulation of autonomic functions. Our results show that the expression of MeCP2 is heterogeneously expressed throughout the postnatal mouse brainstem. MeCP2 expression in each area studied is restricted to neurones. The developmental pattern is mainly characterized by a postnatal decrease of the Mecp2 mRNA and an increase of the MeCP2 protein staining level in spite of the local variability. However, we were not able to correlate the developmental expression of MeCP2 in a given area of the brainstem with autonomic dysfunctions occurring in the presence of a mutation in Mecp2.
甲基化CpG结合蛋白2(MeCP2)是甲基化DNA结合蛋白家族的成员,能够调节靶基因的转录。MECP2突变会导致多种神经学表型,其中最广为人知的疾病是雷特综合征。所有MECP2发生突变的患者均有智力障碍,且大多数患者在由脑干控制的自主神经过程中表现出功能障碍。先前的研究表明,Mecp2在整个啮齿动物大脑中受到发育和空间调控,但均未对脑干进行研究。在本研究中,我们通过实时PCR定量了出生后发育阶段(P0、P7、P21、P35和P55)小鼠脑干不同区域中Mecp2 mRNA的表达水平,并通过免疫定量法定量了MeCP2蛋白的表达水平。我们重点关注了直接参与自主神经功能调节的脑桥和延髓区域。我们的结果表明,MeCP2在出生后小鼠脑干中的表达是异质性的。在所研究的每个区域中,MeCP2的表达仅限于神经元。尽管存在局部差异,但发育模式的主要特征是出生后Mecp2 mRNA减少,而MeCP2蛋白染色水平增加。然而,我们无法将脑干特定区域中MeCP2的发育表达与Mecp2突变时出现的自主神经功能障碍联系起来。