Podocyte-Specific Deletion of Murine CXADR Does Not Impair Podocyte Development, Function or Stress Response

• Published in: PloS one Vol. 10; no. 6; p. e0129424
• Main Authors: Schell, Christoph, Kretz, Oliver, Bregenzer, Andreas, Rogg, Manuel, Helmstädter, Martin, Lisewski, Ulrike, Gotthardt, Michael, Tharaux, Pierre-Louis, Huber, Tobias B, Grahammer, Florian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.06.2015; Public Library of Science (PLoS)
• Subjects: Adenoviruses; Animal models; Animals; Biology; Brain research; Cellular stress response; Clonal deletion; Coxsackie and Adenovirus Receptor-Like Membrane Protein - genetics; Coxsackie and Adenovirus Receptor-Like Membrane Protein - metabolism; Embryos; Epithelial cells; Experiments; Gene Deletion; Gene Expression; Gene Knockout Techniques; Genetic engineering; Injuries; Kidney - embryology; Kidney - metabolism; Kidney Glomerulus - cytology; Kidney Glomerulus - embryology; Kidney Glomerulus - metabolism; Kidney Glomerulus - ultrastructure; Kidneys; Laboratory animals; Lethality; Mammals; Medicine; Mice; Mice, Knockout; Microscopy; Neurosciences; Pattern formation; Phenotypes; Physiology; Podocytes - metabolism; Proteins; Rodents; Stress response; Stress, Physiological; Transgenic; Urine; Viruses; Zebrafish; France; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0129424

The coxsackie- and adenovirus receptor (CXADR) is a member of the immunoglobulin protein superfamily, present in various epithelial cells including glomerular epithelial cells. Beside its known function as a virus receptor, it also constitutes an integral part of cell-junctions. Previous studies in the zebrafish pronephros postulated a potential role of CXADR for the terminal differentiation of glomerular podocytes and correct patterning of the elaborated foot process architecture. However, due to early embryonic lethality of constitutive Cxadr knockout mice, mammalian data on kidney epithelial cells have been lacking. Interestingly, Cxadr is robustly expressed during podocyte development and in adulthood in response to glomerular injury. We therefore used a conditional transgenic approach to elucidate the function of Cxadr for podocyte development and stress response. Surprisingly, we could not discern a developmental phenotype in podocyte specific Cxadr knock-out mice. In addition, despite a significant up regulation of CXADR during toxic, genetic and immunologic podocyte injury, we could not detect any impact of Cxadr on these injury models. Thus these data indicate that in contrast to lower vertebrate models, mammalian podocytes have acquired molecular programs to compensate for the loss of Cxadr.