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Double gene deletion reveals lack of cooperation between claudin 11 and claudin 14 tight junction proteins

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Abstract

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.

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Acknowledgments

We thank Thomas Friedman for the anti-prestin and anti-claudin 14 antibodies, Karen Avraham for the use of her ABR system, Hoda Awad for technical assistance, and Thomas Friedman and James Anderson for critical reading of this manuscript.

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Authors and Affiliations

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

    Liron Elkouby-Naor & Tamar Ben-Yosef

  2. 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

    Zaid Abassi

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

    Ayala Lagziel

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

    Alexander Gow

  5. Department of Genetics, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Bat Galim, Haifa, 31096, Israel

    Tamar Ben-Yosef

Authors
  1. Liron Elkouby-Naor
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  2. Zaid Abassi
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  3. Ayala Lagziel
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  4. Alexander Gow
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  5. Tamar Ben-Yosef
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Correspondence to Tamar Ben-Yosef.

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This work was supported by the Israel Science Foundation (grant no. 24/05) and by NIDCD/NIH intramural research funds (Z01-DC-00039–11).

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Elkouby-Naor, L., Abassi, Z., Lagziel, A. et al. Double gene deletion reveals lack of cooperation between claudin 11 and claudin 14 tight junction proteins. Cell Tissue Res 333, 427–438 (2008). https://doi.org/10.1007/s00441-008-0621-9

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