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 lamini n B1/beta 1 chain, is a major component of adult renal glomerular base ment membrane (GEM). Immature GEM bears beta 1, which is replaced by b eta 2 as development proceeds. In mutant mice that lack beta 2, the GE M remains rich in beta 1, suggesting that a feedback mechanism normall y regulates GEM maturation. The beta 2-deficient GEM is structurally i ntact and contains normal complements of several collagenous acid nonc ollagenous glycoproteins. However, mutant mice develop massive protein uria due to failure of the glomerular filtration barrier. These result s support the idea that laminin beta chains are functionally distinct although they assemble to form similar structures. Laminin beta 2-defi cient mice may provide a model for human congenital or idiopathic neph rotic syndromes.