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首页> 外文期刊>Cell and Tissue Research >Double gene deletion reveals lack of cooperation between claudin 11 and claudin 14 tight junction proteins
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Double gene deletion reveals lack of cooperation between claudin 11 and claudin 14 tight junction proteins

机译:双基因缺失显示claudin 11和claudin 14紧密连接蛋白之间缺乏合作

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摘要

Members of the claudin family of proteins are the main components of tight junctions (TJs), the major selective barrier of the paracellular pathway between epithelial cells. The selectivity and specificity of TJ strands are determined by the type of claudins present. An understanding of the cooperation between different claudins in various tissues is thus important. To study the possible cooperation between claudin 11 and claudin 14, we have generated claudin 11/claudin 14 double-deficient mice, which exhibit a combination of the phenotypes found in each of the singly deficient mutants, including deafness, neurological deficits, and male sterility. These two claudins have distinct and partially overlapping expression patterns in the kidney. Claudin 11 is located in both the proximal and distal convoluted tubules, whereas claudin 14 occurs in both the thin descending and thick ascending limbs of the loop of Henle and in the proximal convoluted tubules. Although daily urinary excretion of Mg++, and to a lesser extent of Ca++, tends to be higher in claudin 11/claudin 14 double mutants, these changes do not reach statistical significance compared with wild-type animals. Thus, under normal conditions, co-deletion of claudin 11 and claudin 14 does not affect kidney function or ion balance. Our data demonstrate that, despite the importance of each of these claudins, there is probably no functional cooperation between them. Generation of additional mouse models in which different claudins are abolished should provide further insight into the complex interactions between claudin proteins in various physiological systems.
机译:claudin家族的成员是紧密连接(TJs)的主要成分,紧密连接是上皮细胞之间副细胞途径的主要选择性屏障。 TJ链的选择性和特异性由存在的claudin的类型决定。因此,重要的是了解各种组织中不同claudin之间的协同作用。为了研究claudin 11和claudin 14之间可能的合作,我们产生了claudin 11 / claudin 14双缺陷小鼠,它们表现出在每个单缺陷突变体中都存在的表型组合,包括耳聋,神经系统缺陷和雄性不育。这两个claudins在肾脏中具有不同且部分重叠的表达模式。克劳丁11位于近端和远端的螺旋小管中,而claudin 14则出现在Henle环的薄的下降和较厚的上升分支中以及近端的曲折的小管中。尽管claudin 11 / claudin 14双重突变体中的Mg ++ 和Ca ++ 的每日尿排泄量较高,但与野生型动物相比,这些变化没有统计学意义。因此,在正常情况下,claudin 11和claudin 14的共同缺失不会影响肾脏功能或离子平衡。我们的数据表明,尽管每个claudins都很重要,但它们之间可能没有功能上的合作。消除了不同claudin的其他小鼠模型的产生,应该可以进一步了解各种生理系统中claudin蛋白之间的复杂相互作用。

著录项

  • 来源
    《Cell and Tissue Research》 |2008年第3期|427-438|共12页
  • 作者单位

    Department of Genetics The Rappaport Family Institute for Research in the Medical Sciences Faculty of Medicine Technion-Israel Institute of Technology Haifa Israel;

    Department of Physiology and Biophysics The Rappaport Family Institute for Research in the Medical Sciences Faculty of Medicine Technion-Israel Institute of Technology Haifa Israel;

    Section on Human Genetics Laboratory of Molecular Genetics National Institute on Deafness and Other Communication Disorders National Institutes of Health Rockville Md. USA;

    Center for Molecular Medicine and Genetics Carman and Ann Adams Department of Pediatrics Department of Neurology Wayne State University Detroit Mich. USA;

    Department of Genetics The Rappaport Family Institute for Research in the Medical Sciences Faculty of Medicine Technion-Israel Institute of Technology Haifa Israel;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Tight junction; Claudin 11; Claudin 14; Knockout mouse;

    机译:紧密连接;克劳丁11;克劳丁14;敲除小鼠;

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