G.P.4 A comparison of the structural brain defects in dystroglycanopathy mouse models

Abstract

Mutations in several genes encoding for either determined or putative glycosyltransferases are associated with the hypoglycosylation of α-dystroglycan, which effectively disrupts the linkage between the dystrophin-associated glycoprotein complex and the extracellular matrix. These mutations are responsible for a clinically heterogenous group of muscular dystrophies, which vary in severity from severe congenital muscular dystrophies, with substantial brain and eye involvement, to relatively mild adult-onset limb girdle muscular dystrophies. The underlying reason for the spectrum of defects, ranging from complete lissencephaly in patients with Walker–Warburg syndrome to isolated cerebellar involvement is at present unclear. In order to further investigate this aspect we have undertaken a comparative study of structural brain involvement in different dystroglycanopathy mouse models, with a particular emphasis on the deposition of the pial basement membrane. Our data indicate that several processes contribute to the disease process and that there are important differences between models.