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.

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Authors

Jarad G, Pippin JW, Shankland SJ, Kreidberg JA, Miner JH

Institution

Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA.

Source

American journal of physiology. Renal physiology 300:3 2011 Mar pg F811-20

MeSH

Acute Kidney Injury
Animals
Dystroglycans
Epithelial Cells
Integrases
Integrin alpha3
Kidney
Kidney Glomerulus
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Models, Animal
Podocytes

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21209007