title: CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility.
abstract: Loss of CD2-associated protein (CD2AP), a component of the filtration complex in the kidney, causes death in mice at 6 weeks of age. Mice with CD2AP haploinsufficiency developed glomerular changes at 9 months of age and had increased susceptibility to glomerular injury by nephrotoxic antibodies or immune complexes. Electron microscopic analysis of podocytes revealed defects in the formation of multivesicular bodies, suggesting an impairment of the intracellular degradation pathway. Two human patients with focal segmental glomerulosclerosis had a mutation predicted to ablate expression of one CD2AP allele, implicating CD2AP as a determinant of human susceptibility to glomerular disease.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jeong M
authors.initials: JM
authors.lastname: Kim
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Gopa
authors.initials: G
authors.lastname: Green
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miner
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000936:Antigen-Antibody Complex; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003598:Cytoskeletal Proteins; D004705:Endocytosis; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology; D005091:Exons; D005293:Ferritins / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D011507:Proteinuria / Q000209:etiology; D012326:RNA Splicing
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000936:Antigen-Antibody Complex; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D007136:Immunoglobulins; D011506:Proteins; D005293:Ferritins