Deletion of CD151 results in a strain-dependent glomerular disease due to severe alterations of the glomerular basement membrane.
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 alpha3beta1-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 alpha3-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.
Baleato
Rosa M
RM
School of Biomedical Sciences and Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
Guthrie
Petrina L
PL
Gubler
Marie-Claire
MC
Ashman
Leonie K
LK
Roselli
Séverine
S
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D050533:Glomerular Basement Membrane / Q000473:pathology* / Q000648:ultrastructure; D007674:Kidney Diseases / Q000473:pathology*; D008297:Male; D051379:Mice; D050199:Podocytes / Q000473:pathology / Q000648:ultrastructure; D021381:Protein Transport; D011507:Proteinuria / Q000473:pathology; D013045:Species Specificity; D060185:Tetraspanin 24
D015703:Antigens, CD; C554715:CD151 protein, human; C554716:Cd151 protein, mouse; D060185:Tetraspanin 24
J Clin Invest. 2006 Aug;116(8):2272-9
16886065
Nat Clin Pract Nephrol. 2006 May;2(5):271-82
16932440
J Biol Chem. 2002 Oct 4;277(40):36991-7000
12110679
Am J Pathol. 2003 Oct;163(4):1633-44
14507670
Mol Cell Biol. 2004 Jul;24(13):5978-88
15199151
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7616-21
12805567
Kidney Int Suppl. 1995 Jun;49:S29-33
7674589
J Cell Sci. 1999 Mar;112 ( Pt 6):833-44
10036233
Nephrol Dial Transplant. 2003 Oct;18(10):1999-2004
13679473
J Am Soc Nephrol. 2006 May;17(5):1334-44
16611717
J Cell Biol. 2002 Jun 24;157(7):1279-90
12082085
J Cell Biol. 2006 Oct 9;175(1):33-9
17015618
Biochem J. 1999 May 15;340 ( Pt 1):103-11
10229664
J Cell Sci. 2002 Mar 15;115(Pt 6):1161-73
11884516
Mol Cell Biol. 2004 Jan;24(2):550-60
14701729
Biochem J. 2000 Nov 1;351 Pt 3:629-37
11042117
Blood. 2004 Oct 15;104(8):2368-75
15226180
J Cell Biol. 1997 May 5;137(3):685-701
9151674
Histochem Cell Biol. 1995 Oct;104(4):267-75
8548560
J Biol Chem. 1993 Dec 15;268(35):26033-6
8253711
Eur J Biochem. 2002 Jan;269(2):431-42
11856301
J Invest Dermatol. 2006 Mar;126(3):680-9
16410781
Am J Pathol. 2006 Jan;168(1):42-54
16400008
Development. 1996 Nov;122(11):3537-47
8951069
Mol Biol Cell. 1998 Oct;9(10):2751-65
9763442
J Histochem Cytochem. 1997 Apr;45(4):515-25
9111230
J Histochem Cytochem. 1993 Aug;41(8):1273-8
7687266
Am J Pathol. 2002 Feb;160(2):721-30
11839593
Dev Biol. 2008 Jan 15;313(2):584-93
18082680
Nephrol Dial Transplant. 1997 Jun;12(6):1238-41
9198058
J Cell Biol. 1999 Jul 26;146(2):477-92
10427099
J Cell Biol. 1997 May 5;137(3):729-42
9151677
Mol Biol Cell. 1996 Feb;7(2):193-207
8688552
Blood. 2004 Oct 15;104(8):2217-23
15265795
Hum Mol Genet. 2004 Nov 1;13(21):2625-32
15367484
J Biol Chem. 2007 Oct 26;282(43):31631-42
17716972
Am J Pathol. 2002 Jan;160(1):131-9
11786407
Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1939-44
15677332
Nephrol Dial Transplant. 2006 Mar;21(3):591-7
16326737