title: Podocyte-Specific Deletion of Murine CXADR Does Not Impair Podocyte Development, Function or Stress Response.
abstract: 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.
authors.affiliation: Renal Division, University Medical Center Freiburg, Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs University Freiburg, Freiburg, Germany; Faculty of Biology, Albert-Ludwigs University Freiburg, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schell
authors.affiliation: Renal Division, University Medical Center Freiburg, Freiburg, Germany; Department of Neuroanatomy, Albert-Ludwigs University Freiburg, Freiburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kretz
authors.affiliation: Renal Division, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bregenzer
authors.affiliation: Renal Division, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rogg
authors.affiliation: Renal Division, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Helmstädter
authors.affiliation: Max-Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lisewski
authors.affiliation: Max-Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gotthardt
authors.affiliation: Paris Centre de Recherche Cardiovasculaire, INSERM, Paris, France.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Tharaux
authors.affiliation: Renal Division, University Medical Center Freiburg, Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs University Freiburg, Freiburg, Germany; BIOSS Center for Biological Signaling Studies, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Huber
authors.affiliation: Renal Division, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Grahammer
mesh_terms: D000818:Animals; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D055786:Gene Knockout Techniques; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D050199:Podocytes / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein