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 lamini n alpha 2 chain in brain and localize the alpha 2 protein to the capil lary basement membrane. While in peripheral basement membranes the lam inin alpha 1 and alpha 2 chains have an almost mutually exclusive dist ribution, 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 th e capillary basement membrane in dystrophic dy mice, which show a 70-9 0% and >95% reduction of alpha 2 messenger RNA compared to heterozygou s 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 st ructural basement membrane abnormalities, the present results show tha t the lack of the alpha 2 subunit in the cerebral capillary basement m embrane is not detrimental to its structure. This observation might be explained by the fact that the cerebral capillary basement membrane e xpresses both a chains and therefore exhibits structural redundancy.