Visual impairment in the absence of dystroglycan.
Ocular involvement in muscular dystrophy ranges from structural defects to abnormal electroretinograms. While the mechanisms underlying the abnormal retinal physiology in patients are not understood, it is thought that alpha-dystroglycan extracellular interactions are critical for normal visual function. Here we show that beta-dystroglycan anchors dystrophin and the inward rectifying K(+) channel Kir4.1 at glial endfeet and that disruption of dystrophin and potassium channel clustering in dystroglycan mutant mice is associated with an attenuation of the electroretinogram b-wave. Glial-specific inactivation of dystroglycan or deletion of the cytoplasmic domain of beta-dystroglycan was sufficient to attenuate the electroretinogram b-wave. Unexpectedly, deletion of the beta-dystroglycan cytoplasmic domain did not disrupt the laminar structure of the retina. In contrast to the role of alpha-dystroglycan extracellular interactions during early development of the CNS, beta-dystroglycan intracellular interactions are important for visual function but not the laminar development of the retina.
Satz
Jakob S
JS
Department of Molecular Physiology and Biophysics, Roy J and Lucille A Carver College of Medicine, Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA.
Philp
Alisdair R
AR
Nguyen
Huy
H
Kusano
Hajime
H
Lee
Jane
J
Turk
Rolf
R
Riker
Megan J
MJ
Hernández
Jasmine
J
Weiss
Robert M
RM
Anderson
Michael G
MG
Mullins
Robert F
RF
Moore
Steven A
SA
Stone
Edwin M
EM
Campbell
Kevin P
KP
D000818:Animals; D049030:Dystroglycans / Q000172:deficiency*; D016189:Dystrophin / Q000378:metabolism; D004596:Electroretinography / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D010775:Photic Stimulation / Q000379:methods; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology; D014786:Vision Disorders / Q000235:genetics* / Q000503:physiopathology*; D014794:Visual Fields / Q000235:genetics; D000098854:Kcnj10 Channel
D016189:Dystrophin; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D000098854:Kcnj10 Channel; D007797:Laminin; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D024661:Potassium Channels, Inwardly Rectifying; D049030:Dystroglycans