Laminin alpha 2 is a component of brain capillary basement membrane: reduced expression in dystrophic dy mice.
In the present study we demonstrate low level expression of the laminin alpha 2 chain in brain and localize the alpha 2 protein to the capillary basement membrane. While in peripheral basement membranes the laminin alpha 1 and alpha 2 chains have an almost mutually exclusive distribution, the present results suggest both alpha 1 and alpha 2 in the cerebral capillary basement membrane. Towards elucidating the function of alpha 2 in brain, we have performed ultrastructural analysis of the capillary basement membrane in dystrophic dy mice, which show a 70-90% and > 95% reduction of alpha 2 messenger RNA compared to heterozygous and wild-type mice, respectively, and show a nearly total absence of the alpha 2 protein by immunofluorescence. In contrast to the muscle and Schwann cell basement membrane, where alpha 2 deficiency causes structural basement membrane abnormalities, the present results show that the lack of the alpha 2 subunit in the cerebral capillary basement membrane is not detrimental to its structure. This observation might be explained by the fact that the cerebral capillary basement membrane expresses both alpha chains and therefore exhibits structural redundancy.
Jucker
M
M
Molecular Neurobiology Unit, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Tian
M
M
Norton
D D
DD
Sherman
C
C
Kusiak
J W
JW
D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D001485:Basement Membrane / Q000737:chemistry* / Q000648:ultrastructure; D015152:Blotting, Northern; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002196:Capillaries / Q000737:chemistry* / Q000648:ultrastructure; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009137:Muscular Dystrophy, Animal / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
D007797:Laminin; D012333:RNA, Messenger