Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/43152

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Title
Deletion of Cd151 results in a strain-dependent glomerular disease due to severe alterations of the glomerular basement membrane
Author/Creator
Baleato, Rosa;  Guthrie, Petrina L.;  Gubler, Marie-Claire;  Ashman, Leonie K.;  Roselli, Severine
Institution
The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
Description
Alterations in CD151 have been associated with primary glomerular disease in both humans and mice, implicating CD151 as a key component of the glomerular filtration barrier. CD151 belongs to the tetraspanin family and associates with cell-matrix adhesion complexes such as 3β1-integrin. Here we show that Cd151-deficient mice develop severe kidney disease on an FVB background but are healthy on a B6 background, providing a new and unique tool for the identification of genes that modulate the onset of proteinuria. To better understand the function of CD151 in the kidney, we studied its expression pattern and characterized early ultrastructural defects in Cd151-null kidneys. CD151 is expressed in podocytes of the mouse kidney and co-localizes with 3-integrin at the base of podocyte foot processes, at the site of anchorage to the glomerular basement membrane (GBM). Interestingly, the first ultrastructural lesions seen at the onset of proteinuria in Cd151-null kidneys were severe alterations of the GBM, reminiscent of Alport syndrome and consisting of massive thickening and splitting of the GBM. These lesions are associated with increased expression of GBM components. Podocyte abnormalities, effacement of foot processes, and podocyte loss appear to occur consequently to the GBM damage. In conclusion, CD151 appears to be involved in the establishment, maturation, and/or maintenance of the GBM structure in addition to its role in integrin-mediated adhesion strengthening.
Relation
American Journal of Pathology Vol. 173, Issue 4, p. 927-937
Publisher Link
http://dx.doi.org/10.2353/ajpath.2008.071149
Date
2008
Publisher
American Journal of Pathology
Keyword(s)
defined monoclonal antibodies;  transmembrane 3 superfamily;  cell migration;  renal disease;  alpha-3;  beta-1 integrin;  tetraspanin Cd151;  mice lacking;  IV collagen;  integrin;  alpha-3 beta-1;  split diaphragm
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/43152
Identifier
ISSN:0002-9440
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Subject
"American Journal of Pathology"
 
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