title: Deletion of the laminin alpha4 chain leads to impaired microvessel maturation.
abstract: The laminin alpha4 chain, a component of laminin-8 and -9, is expressed in basement membranes, such as those beneath endothelia, the perineurium of peripheral nerves, and around developing muscle fibers. Laminin alpha4-null mice presented with hemorrhages during the embryonic and neonatal period and had extensive bleeding and deterioration of microvessel growth in experimental angiogenesis, as well as mild locomotion defects. Histological examination of newborn mice revealed delayed deposition of type IV collagen and nidogen into capillary basement membranes, and electron microscopy showed discontinuities in the lamina densa. The results demonstrate a central role for the laminin alpha4 chain in microvessel growth and, in the absence of other laminin alpha chains, in the composition of endothelial basement membranes.
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17 177 Stockholm, Sweden.
authors.forename: Jill
authors.initials: J
authors.lastname: Thyboll
authors.forename: Jarkko
authors.initials: J
authors.lastname: Kortesmaa
authors.forename: Renhai
authors.initials: R
authors.lastname: Cao
authors.forename: Raija
authors.initials: R
authors.lastname: Soininen
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Antti
authors.initials: A
authors.lastname: Iivanainen
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.forename: Mårten
authors.initials: M
authors.lastname: Risling
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
mesh_terms: D000740:Anemia; D000818:Animals; D000831:Animals, Newborn; D001485:Basement Membrane / Q000737:chemistry / Q000648:ultrastructure; D002196:Capillaries / Q000196:embryology / Q000254:growth & development* / Q000648:ultrastructure; D003094:Collagen / Q000032:analysis; D003315:Cornea / Q000098:blood supply; D016510:Corneal Neovascularization; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006470:Hemorrhage; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000737:chemistry; D020033:Protein Isoforms
chemical_list: C501370:Lama4 protein, mouse; D007797:Laminin; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; C029967:nidogen; D016222:Fibroblast Growth Factor 2; D003094:Collagen