Abnormal glomerular basement membrane laminins in murine, canine, and human Alport syndrome: aberrant laminin alpha2 deposition is species independent.
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.
Kashtan
Clifford E
CE
Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota.
Kim
Youngki
Y
Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota.
Lees
George E
GE
Texas Veterinary Medical Center, Texas A&M University, College Station, Texas.
Thorner
Paul S
PS
Division of Pathology, Hospital for Sick Children and University of Toronto, Toronto, Canada.
Virtanen
Ismo
I
Department of Anatomy, University of Helsinki, Institute of Biomedicine, Helsinki, Finland.
Miner
Jeffrey H
JH
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D004285:Dogs; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D008297:Male; D009394:Nephritis, Hereditary / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity
D007797:Laminin; C102645:laminin alpha 2; C097043:laminin alpha5; C058783:laminin beta2