THE RENAL GLOMERULUS OF MICE LACKING S-LAMININ LAMININ BETA-2 - NEPHROSIS DESPITE MOLECULAR COMPENSATION BY LAMININ BETA-1

S-laminin/laminin beta 2, a homologue of the widely distributed laminin B1/beta 1 chain, is a major component of adult renal glomerular basement membrane (GEM). Immature GEM bears beta 1, which is replaced by beta 2 as development proceeds. In mutant mice that lack beta 2, the GEM remains rich in beta 1, suggesting that a feedback mechanism normally regulates GEM maturation. The beta 2-deficient GEM is structurally intact and contains normal complements of several collagenous acid noncollagenous glycoproteins. However, mutant mice develop massive proteinuria due to failure of the glomerular filtration barrier. These results support the idea that laminin beta chains are functionally distinct although they assemble to form similar structures. Laminin beta 2-deficient mice may provide a model for human congenital or idiopathic nephrotic syndromes.