Distribution of potassium ion and water permeable channels at perivascular glia in brain and retina of the Largemyd mouse

The dystroglycan protein complex provides a link between the cytoskeleton and the extracellular matrix (ECM). Defective O-glycosylation of α-dystroglycan (α-DG) severs this link leading to muscular dystrophies named dystroglycanopathies. These are characterized not only by muscle degeneration, but also by brain and ocular defects. In brain and retina, α-DG and ECM molecules are enriched around blood vessels where they may be involved in localizing the inwardly rectifying potassium channel, Kir4.1, and aquaporin channel, AQP4, to astrocytic endfeet. To investigate in vivo the role of ECM ligand-binding to glycosylated sites on α-DG in the polarized distribution of these channels, we used the Largemyd mouse, an animal model for dystroglycanopathies. We found that Kir4.1 and AQP4 are lost from astrocytic endfeet in brain whereas significant labeling for these channels is detected at similar cell domains in retina. Furthermore, while both α- and β1-syntrophins are lost from perivascular astrocytes in brain, labeling for β1-syntrophin is found in retina of the Largemyd mouse. These findings show that while ligand-binding to the highly glycosylated isoform of α-DG in concert with α- and β1-syntrophins is crucial for the polarized distribution of Kir4.1 and AQP4 to functional domains in brain, distinct mechanisms may contribute to their localization in retina.