Abnormal glomerular basement membrane laminins in murine, canine, and human Alport syndrome: aberrant laminin alpha2 deposition is species independent.

Abstract

Kidneys from mice, dogs, and humans with X-linked and autosomal-recessive forms of Alport syndrome were examined by immunofluorescence for expression of laminin alpha, beta, and gamma chains using monospecific antibodies. Laminin alpha2 chain was absent from glomerular basement membranes (GBM) in normal human, murine, and canine kidneys but was abnormally deposited in Alport GBM, regardless of species or inheritance pattern. In murine and canine Alport kidneys, laminin alpha2 seems to be deposited as part of both laminin-2 (alpha2beta1gamma1) and laminin-4 (alpha2beta2gamma1) but as part of only laminin-4 in human Alport kidneys. GBM laminin alpha2 chain deposition was not observed in a variety of non-Alport human glomerulopathies. This finding adds to the list of proteins that are aberrantly deposited in Alport GBM as a consequence of the absence of the alpha3, alpha4, and alpha5 chains of type IV collagen: (1) type IV collagen alpha1 and alpha2 chains, (2) type V collagen, (3) type VI collagen, and most recently (4) the laminin alpha2 chain and (5) the laminin alpha1 and beta1 chains in mice and dogs. These findings emphasize further the critical role played by the alpha3, alpha4, and alpha5 chains of type IV collagen in establishing and maintaining the composition, structure, and function of mature GBM.