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Am J Physiol Renal Physiol 294: F393-F406, 2008. First published November 21, 2007; doi:10.1152/ajprenal.00315.2007
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Genetic inactivation of the laminin {alpha}5 chain receptor Lu/BCAM leads to kidney and intestinal abnormalities in the mouse

Cécile Rahuel,1 Anne Filipe,1,* Léa Ritie,2,* Wassim El Nemer,1 Natacha Patey-Mariaud,3 Dominique Eladari,4 Jean-Pierre Cartron,1 Patricia Simon-Assmann,2 Caroline Le Van Kim,1 and Yves Colin1

1Institut National de la Santé et de la Recherche Médicale, Unité 665, Institut National de la Transfusion Sanguine, and University Paris Diderot, Paris, France; 2Institut National de la Santé et de la Recherche Médicale, Unité 682, University Louis Pasteur, Strasbourg; 3Service de Néphrologie, Hôpital Necker-Enfants Malades; and 4Institut National de la Santé et de la Recherche Médicale, Unité 872, Paris, France

Submitted 10 July 2007 ; accepted in final form 13 November 2007

Lutheran blood group and basal cell adhesion molecule (Lu/BCAM) has been recognized as a unique receptor for laminin {alpha}5 chain in human red blood cells and as a coreceptor in epithelial, endothelial, and smooth muscle cells. Because limited information is available regarding the function of this adhesion glycoprotein in vivo, we generated Lu/BCAM-null mice and looked for abnormalities in red blood cells as well as in kidney and intestine, two tissues showing alteration in laminin {alpha}5 chain-deficient mice. We first showed that, in contrast to humans, wild-type murine red blood cells failed to express Lu/BCAM. Lu/BCAM-null mice were healthy and developed normally. However, although no alteration of the renal function was evidenced, up to 90% of the glomeruli from mutant kidneys exhibited abnormalities characterized by a reduced number of visible capillary lumens and irregular thickening of the glomerular basement membrane. Similarly, intestine analysis of mutant mice revealed smooth muscle coat thickening and disorganization. Because glomerular basement membrane and smooth muscle coat express laminin {alpha}5 chain and are in contact with cell types expressing Lu/BCAM in wild-type mice, these results provide evidence that Lu/BCAM, as a laminin receptor, is involved in vivo in the maintenance of normal basement membrane organization in the kidney and intestine.

lutheran blood group and basal cell adhesion molecule; basement membranes; glomeruli; intestine; knockout mice



Address for reprint requests and other correspondence: Y. Colin, INSERM U665, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75015 Paris, France (e-mail: colin{at}idf.inserm.fr)




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