Abnormal Glomerular Basement Membrane Laminins in Murine, Canine, and Human Alport Syndrome: Aberrant Laminin α2 Deposition Is Species Independent

Abstract

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 α, β, and γ chains using monospecific antibodies. Laminin α2 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 α2 seems to be deposited as part of both laminin-2 (α2β1γ1) and laminin-4 (α2β2γ1) but as part of only laminin-4 in human Alport kidneys. GBM laminin α2 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 α3, α4, and α5 chains of type IV collagen: (1) type IV collagen α1 and α2 chains, (2) type V collagen, (3) type VI collagen, and most recently (4) the laminin α2 chain and (5) the laminin α1 and β1 chains in mice and dogs. These findings emphasize further the critical role played by the α3, α4, and α5 chains of type IV collagen in establishing and maintaining the composition, structure, and function of mature GBM.