Dp260 disrupted mice revealed prolonged implicit time of the b-wave in ERG and loss of accumulation of beta-dystroglycan in the outer plexiform layer of the retina.
Dp260 is a C-terminal isoform of dystrophin and is expressed specifically in the retina. Abnormal electroretinograms (ERG) in some Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients are likely linked to a disruption of Dp260. To clarify the importance of Dp260 in the retina, we examined dystrophin exon 52 knock-out mice, whose expression of Dp260 is impaired. We also confirmed the localization of Dp260 in the outer plexiform layer (OPL) of the retina. Disruption of Dp260 causes a change in the localization of beta-dystroglycan, which is normally found in the OPL of the retina. This suggests a requirement for Dp260 for normal formation of the dystrophin-dystroglycan complex in the retina. Dp71, also expressed in the retina, was, however, not detected in the OPL. The difference in localization of Dp260 and Dp71 implies that the two isoforms have different functions. The dystrophin exon 52 knock-out mice had a prolonged implicit time of the b-wave in ERG, although no significant change was observed in amplitude. These ERG findings differed from those of DMD and BMD patients, especially with regard to amplitude of the b-wave, but make it clear that Dp260 is required for normal electrophysiology.
Kameya
S
S
Department of Molecular Genetics, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187, Japan.
Araki
E
E
Katsuki
M
M
Mizota
A
A
Adachi
E
E
Nakahara
K
K
Nonaka
I
I
Sakuragi
S
S
Takeda
S
S
Nabeshima
Y
Y
D000818:Animals; D003598:Cytoskeletal Proteins / Q000172:deficiency*; D049030:Dystroglycans; D016189:Dystrophin / Q000235:genetics / Q000502:physiology*; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D012160:Retina / Q000737:chemistry* / Q000503:physiopathology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology*
D003598:Cytoskeletal Proteins; C484607:Dp260 protein, mouse; D016189:Dystrophin; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D049030:Dystroglycans