title: Structurally altered basement membranes and hydrocephalus in a type XVIII collagen deficient mouse line.
abstract: Type XVIII collagen/endostatin is known to be crucial for the eye, as witnessed by severe eye defects in Knobloch syndrome patients with mutations in this collagen and in Col18a1(-/-) mice. We show here that in a specific C57BL background, 20% of the Col18a1(-/-) mice developed hydrocephalus, and dilation of the brain ventricles was observed by MRI in all of the mutant mice. Significant broadening was observed in the epithelial basement membrane (BM) of the choroid plexuses (CP), its width being 86.4+/-10.52 nm, compared with 61.4+/-6.05 nm in wild-type mice. The CP epithelial cell morphology was balloon-shaped rather than cuboidal, and the microvilli of the apical surface of the CP epithelium contained more vacuoles in the null mice than in the wild-type, as also did the CP epithelial cells, which is suggestive of alterations in cerebrospinal fluid production. Analysis of BMs elsewhere in the body revealed a broadened epidermal BM in the Col18a1(-/-) mice, but this did not result in any apparent functional deficiencies. Moreover, markedly broadened BMs were found in the atrioventricular valves of the heart and in the kidney tubules, whereas the glomerular mesangial matrix of the kidneys was expanded in the mutant mice and serum creatinine levels were elevated, indicating alterations in kidney filtration capacity. We thus suggest that type XVIII collagen is a structurally important constituent of BMs, and that its absence can result in a variety of phenotypic alterations.
authors.affiliation: Collagen Research Unit, Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, 90014 Oulu, Finland.
authors.forename: Aino
authors.initials: A
authors.lastname: Utriainen
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.forename: Mikko
authors.initials: M
authors.lastname: Kettunen
authors.forename: Lorenza S
authors.initials: LS
authors.lastname: Carvalhaes
authors.forename: Esko
authors.initials: E
authors.lastname: Sajanti
authors.forename: Lauri
authors.initials: L
authors.lastname: Eklund
authors.forename: Risto
authors.initials: R
authors.lastname: Kauppinen
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Kitten
authors.forename: Taina
authors.initials: T
authors.lastname: Pihlajaniemi
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000473:pathology / Q000648:ultrastructure; D002552:Cerebral Ventricles / Q000002:abnormalities; D002831:Choroid Plexus / Q000276:immunology / Q000473:pathology; D043170:Collagen Type XVIII / Q000032:analysis / Q000172:deficiency / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D043169:Endostatins / Q000032:analysis / Q000378:metabolism; D004848:Epithelium / Q000473:pathology / Q000648:ultrastructure; D005920:Glomerular Mesangium / Q000473:pathology; D006351:Heart Valves / Q000002:abnormalities / Q000473:pathology; D006849:Hydrocephalus / Q000235:genetics* / Q000473:pathology*; D007668:Kidney / Q000002:abnormalities; D008279:Magnetic Resonance Imaging; D051379:Mice; D008817:Mice, Mutant Strains
chemical_list: D043170:Collagen Type XVIII; D043169:Endostatins; D003404:Creatinine