Deletion of the laminin alpha4 chain leads to impaired microvessel maturation.
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.
Thyboll
Jill
J
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17 177 Stockholm, Sweden.
Kortesmaa
Jarkko
J
Cao
Renhai
R
Soininen
Raija
R
Wang
Ling
L
Iivanainen
Antti
A
Sorokin
Lydia
L
Risling
Mårten
M
Cao
Yihai
Y
Tryggvason
Karl
K
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
C501370:Lama4 protein, mouse; D007797:Laminin; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; C029967:nidogen; D016222:Fibroblast Growth Factor 2; D003094:Collagen