Dystroglycan does not contribute significantly to kidney development or function, in health or after injury

George Jarad, Jeffrey W. Pippin, Stuart J. Shankland, Jordan A. Kreidberg, Jeffrey H. Miner

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Dystroglycan (DG or DAG1) is considered a critical link between the basement membrane and the cytoskeleton in multiple tissues. DG consists of two subunits, an extracellular α-subunit that binds laminin and other basement membrane components, and a transmembrane β-subunit. DG-null mouse embryos die during early embryogenesis because DG is required for Reichert's membrane formation. DG also forms an integral part of the dystrophin-glycoprotein complex in muscle. Although no human DG mutations have been reported, multiple forms of muscular dystrophy have been linked to DG glycosylation defects, and targeted deletion of muscle DG causes muscular dystrophy in mice. Moreover, DG is widely distributed in endothelial and epithelial cells, including those in the kidney. There has therefore been significant interest in DG's role in the kidney, especially in podocytes. Previous reports suggested that DG's disturbance in podocytes might cause glomerular filtration barrier abnormalities. To fully understand DG's contribution to nephrogenesis and kidney function, we used a conditional DG allele and a variety of Cre mice to systematically delete DG from podocytes, ureteric bud, metanephric mesenchyme, and then from the whole kidney. Surprisingly, none of these conditional deletions resulted in significant morphological or functional abnormalities in the kidney. Furthermore, DG-deficient podocytes did not show increased susceptibility to injury, and DG-deficient kidneys did not show delayed recovery. Integrins are therefore likely the primary extracellular matrix receptors in renal epithelia.

Original languageEnglish
Pages (from-to)F811-F820
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number3
DOIs
StatePublished - Mar 1 2011

Keywords

  • Basement membrane
  • Integrin
  • Kidney injury
  • Podocyte

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