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.

Cell-cell communication mediated by the CAR subgroup of immunoglobulin cell adhesion molecules in health and disease

“…These epithelial cells are located in the Bowman's capsule of the kidney and CAR expression is found already at E15 during murine embryogenesis until adulthood. However, specific deletion of CAR in podocytes did not reveal any impairment in structure and function of the renal filter barrier (Schell et al, 2015).…”

“…Although, CAR is also found in germ cells and Sertoli cells of the testes conditional testicular depletion of CAR revealed no severe impairments in the fertility and the blood-testis-barrier (Mirza et al, 2006;Sultana et al, 2014;Tomko et al, 2000;Wang et al, 2007). No influences of CAR absence were observed during the development of podocytes (Schell et al, 2015). These epithelial cells are located in the Bowman's capsule of the kidney and CAR expression is found already at E15 during murine embryogenesis until adulthood.…”

α-Parvin Defines a Specific Integrin Adhesome to Maintain the Glomerular Filtration Barrier

“…Respective colonies were maintained on a C57BL/6 mixed background. Animal models for nephrotoxic serum nephritis, Epb41l5 fl/fl *Nphs1-rtTA-3G*tetOCre , and Nphs2 R231Q/A286V were generated and described previously 34 – 36 . All mouse experiments were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and the German law governing the welfare of animals.…”

EPB41L5 controls podocyte extracellular matrix assembly by adhesome-dependent force transmission

“…Mice were maintained on a SV129 background. Tissue samples from well-established glomerular disease models (Adriamycin (ADR), and NWASP knockout mice) were previously described (Schell et al, 2013(Schell et al, , 2015. Mice were housed in a SPF facility with free access to chow (Kliba-NAFAG, standard chow -3807.PM.L15), water and kept at 12 hour day/night cycle.…”