PUB - Publikationen an der Universität Bielefeld

Dystroglycan (DG) is an extracellular matrix receptor consisting of an alpha- and a beta-DG subunit encoded by the DAG1 gene. The homozygous mutation (c.2006G>T, p.Cys669Phe) in beta-DG causes Muscle-Eye-Brain disease with multicystic leukodystrophy in humans. In a mouse model of this primary dystroglycanopathy, approximately two-thirds of homozygous embryos fail to develop to term. Mutant mice that are born undergo a normal postnatal development but show a late-onset myopathy with partially penetrant histopathological changes and an impaired performance on an activity wheel. Their brains and eyes are structurally normal, but the localization of mutant beta-DG is altered in the glial perivascular endfeet resulting in a perturbed protein composition of the blood-brain and blood-retina barrier. In addition, alpha- and beta-DG protein levels are significantly reduced in muscle and brain of mutant mice. Due to the partially penetrant developmental phenotype of the C669F-beta-DG mice, they represent a novel and highly valuable mouse model to study the molecular effects of beta-DG functional alterations both during embryogenesis and in mature muscle, brain and eye, and to gain insight into the pathogenesis of primary dystroglycanopathies. © 2024. Published by The Company of Biologists Ltd.