Deletion of Cd151 Results in a Strain-Dependent Glomerular Disease Due to Severe Alterations of the Glomerular Basement Membrane

Rosa M. Baleato^*, Petrina L. Guthrie^*, Marie-Claire Gubler, Leonie K. Ashman^* and Séverine Roselli^*

From the School of Biomedical Sciences and Hunter Medical Research Institute,^* University of Newcastle, Newcastle, NSW, Australia; INSERM U574, Hôpital Necker-Enfants Malades, Paris, France

Alterations in CD151 have been associated with primary glomerulardisease in both humans and mice, implicating CD151 as a keycomponent of the glomerular filtration barrier. CD151 belongsto the tetraspanin family and associates with cell-matrix adhesioncomplexes such as ${alpha}$ 3β1-integrin. Here we show that Cd151-deficientmice develop severe kidney disease on an FVB background butare healthy on a B6 background, providing a new and unique toolfor the identification of genes that modulate the onset of proteinuria.To better understand the function of CD151 in the kidney, westudied its expression pattern and characterized early ultrastructuraldefects in Cd151-null kidneys. CD151 is expressed in podocytesof the mouse kidney and co-localizes with ${alpha}$ 3-integrin at thebase of podocyte foot processes, at the site of anchorage tothe glomerular basement membrane (GBM). Interestingly, the firstultrastructural lesions seen at the onset of proteinuria inCd151-null kidneys were severe alterations of the GBM, reminiscentof Alport syndrome and consisting of massive thickening andsplitting of the GBM. These lesions are associated with increasedexpression of GBM components. Podocyte abnormalities, effacementof foot processes, and podocyte loss appear to occur consequentlyto the GBM damage. In conclusion, CD151 appears to be involvedin the establishment, maturation, and/or maintenance of theGBM structure in addition to its role in integrin-mediated adhesionstrengthening.