%0 Journal Article
%T The missense mutation C667F in murine β-dystroglycan causes embryonic lethality, myopathy and blood-brain barrier destabilization.
%A Tan RL
%A Sciandra F
%A Hübner W
%A Bozzi M
%A Reimann J
%A Schoch S
%A Brancaccio A
%A Blaess S
%J Dis Model Mech
%V 17
%N 6
%D 2024 Jun 1
%M 38616731
%F 5.732
%R 10.1242/dmm.050594
%X Dystroglycan (DG) is an extracellular matrix receptor consisting of an α- and a β-DG subunit encoded by the DAG1 gene. The homozygous mutation (c.2006G>T, p.Cys669Phe) in β-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 β-DG is altered in the glial perivascular end-feet, resulting in a perturbed protein composition of the blood-brain and blood-retina barrier. In addition, α- and β-DG protein levels are significantly reduced in muscle and brain of mutant mice. Owing to the partially penetrant developmental phenotype of the C669F β-DG mice, they represent a novel and highly valuable mouse model with which to study the molecular effects of β-DG functional alterations both during embryogenesis and in mature muscle, brain and eye, and to gain insight into the pathogenesis of primary dystroglycanopathies.