BackgroundRett syndrome is best known due to its severe and devastating symptoms in the central nervous system. It is produced by mutations affecting the Mecp2 gene that codes for a transcription factor. Nevertheless, evidence for MECP2 activity has been reported for tissues other than those of the central nervous system. Patients affected by Rett presented with intestinal affections whose origin is still not known. We have observed that the Mecp2-null mice presented with episodes of diarrhea, and decided to study the intestinal phenotype in these mice.MethodsMecp2-null mice or bearing the conditional intestinal deletion of MECP2 were used. Morphometirc and histologic analysis of intestine, and RT-PCR, western blot and immunodetection were perfomed on intestinal samples of the animals. Electrical parameters of the intestine were determined by Ussing chamber experiments in freshly isolated colon samples.ResultsFirst we determined that MECP2 protein is mainly expressed in cells of the lower part of the colonic crypts and not in the small intestine. The colon of the Mecp2-null mice was shorter than that of the wild-type. Histological analysis showed that epithelial cells of the surface have abnormal localization of key membrane proteins like ClC-2 and NHE-3 that participate in the electroneutral NaCl absorption; nevertheless, electrogenic secretion and absorption remain unaltered. We also detected an increase in a proliferation marker in the crypts of the colon samples of the Mecp2-null mice, but the specific silencing of Mecp2 from intestinal epithelium was not able to recapitulate the intestinal phenotype of the Mecp2-null mice.ConclusionsIn summary, we showed that the colon is severely affected by Mecp2 silencing in mice. Changes in colon length and epithelial histology are similar to those observed in colitis. Changes in the localization of proteins that participate in fluid absorption can explain watery stools, but the exclusive deletion of Mecp2 from the intestine did not reproduce colon changes observed in the Mecp2-null mice, indicating the participation of other cells in this phenotype and the complex interaction between different cell types in this disease.

中文翻译：

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Rett 综合征 Mecp2-null 小鼠模型结肠上皮的严重变化

背景Rett综合征因其在中枢神经系统中的严重和破坏性症状而广为人知。它是由影响编码转录因子的 Mecp2 基因的突变产生的。尽管如此，已经报道了除中枢神经系统以外的其他组织的 MECP2 活性的证据。受 Rett 影响的患者出现肠道疾病，其起源尚不清楚。我们观察到 Mecp2-null 小鼠出现腹泻发作，并决定研究这些小鼠的肠道表型。方法使用 Mecp2-null 小鼠或携带 MECP2 条件性肠道缺失的小鼠。对动物的肠道样本进行了肠道形态学和组织学分析，以及RT-PCR、蛋白质印迹和免疫检测。肠道电参数通过Ussing室实验在新鲜分离的结肠样品中确定。结果首先我们确定MECP2蛋白主要在结肠隐窝下部的细胞中表达，而不在小肠中表达。Mecp2-null 小鼠的结肠比野生型短。组织学分析表明，表面上皮细胞存在异常定位的关键膜蛋白，如参与电中性NaCl吸收的ClC-2和NHE-3；尽管如此，生电的分泌和吸收保持不变。我们还检测到 Mecp2-null 小鼠结肠样本的隐窝中增殖标记物的增加，但肠上皮细胞的 Mecp2 特异性沉默无法概括 Mecp2-null 小鼠的肠道表型。结论总而言之，我们表明结肠受到小鼠 Mecp2 沉默的严重影响。结肠长度和上皮组织学的变化与在结肠炎中观察到的相似。参与液体吸收的蛋白质定位的变化可以解释水样便，但从肠道中排除 Mecp2 并没有重现在 Mecp2 缺失小鼠中观察到的结肠变化，表明其他细胞参与了这种表型和复合体这种疾病中不同细胞类型之间的相互作用。