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紧密连接蛋白在小鼠出生后肠道发育过程中和整个胃肠道中的分析揭示了复杂的表达模式。

Claudin profiling in the mouse during postnatal intestinal development and along the gastrointestinal tract reveals complex expression patterns.

作者信息

Holmes Jennifer L, Van Itallie Christina M, Rasmussen Julia E, Anderson James M

机构信息

Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

出版信息

Gene Expr Patterns. 2006 Aug;6(6):581-8. doi: 10.1016/j.modgep.2005.12.001. Epub 2006 Feb 2.

Abstract

Members of the claudin protein family are key regulators of tight junction selectivity and are implicated in influencing development and cellular differentiation in the intestine and other tissues. The goal of the present study was to profile claudin gene expression and protein location during postnatal development of the mouse jejunum and in the adult mouse gut from duodenum to distal colon as a first step in understanding both normal claudin function and the pathologic implications of altered expression patterns. The relative expression of claudins 1-19 and other tight and adherens junction genes was determined by quantitative RT-PCR from six regions of normal mouse intestine and colon. Immunofluorescent localization was performed for claudins 1-5, 7, 8, 10, 12, 15, and 18. Transcripts for claudins 1-5, 7-13, 17, and 18 were all detected in adult intestine, although their relative abundance differed up to 1000-fold within individual segments. In contrast to the unchanging expression and localization of ZO-1, occludin, and JAM, most claudins were expressed in decreasing or increasing gradients or in more complex patterns along the longitudinal axis of the intestine and the crypt to villus/surface differentiation axis. During neonatal development at days 1, 14, 28, and 90 several claudins showed striking increases or decreases in transcript expression as well as changes in tissue localization along the crypt-villus axis. Claudin-19 was only detected at days 1 and 14. This database provides a resource for investigating regional and developmental differences in permselectivity, crypt to villus/surface differentiation and neoplastic changes along the gut and during postnatal development.

摘要

claudin蛋白家族成员是紧密连接选择性的关键调节因子,与肠道及其他组织的发育和细胞分化有关。本研究的目的是分析小鼠空肠出生后发育过程中以及成年小鼠从十二指肠到远端结肠的肠道中claudin基因表达和蛋白定位,作为了解claudin正常功能以及表达模式改变的病理意义的第一步。通过定量RT-PCR从正常小鼠肠道和结肠的六个区域测定claudin 1-19以及其他紧密连接和黏附连接基因的相对表达。对claudin 1-5、7、8、10、12、15和18进行免疫荧光定位。claudin 1-5、7-13、17和18的转录本在成年肠道中均有检测到,尽管它们在各个节段中的相对丰度差异高达1000倍。与ZO-1、闭合蛋白和连接黏附分子的表达和定位不变相反,大多数claudin沿肠道纵轴以及隐窝到绒毛/表面分化轴以递减或递增梯度或以更复杂的模式表达。在出生后第1、14、28和90天的新生儿发育过程中,几种claudin在转录本表达上显示出显著增加或减少,以及沿隐窝-绒毛轴的组织定位变化。claudin-19仅在第1天和第14天检测到。该数据库为研究肠道通透性选择、隐窝到绒毛/表面分化以及肠道和出生后发育过程中的肿瘤变化的区域和发育差异提供了资源。

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