Dystroglycan expression in the wild type and mdx mouse neural retina: synaptic colocalization with dystrophin, dystrophin-related protein but not laminin.
Alpha- and beta-dystroglycan (alpha- and beta-DG) are members of a dystrophin-associated glycoprotein complex (DGC) in skeletal muscle which binds to agrin and laminin, and has been postulated to be involved in myoneural snyapse formation. The absence of functional dystrophin in Duchenne muscular dystrophy (DMD) and in one of its animal models, the mdx mouse, leads to a reduction of alpha- and beta-DG in muscle, and is often associated with mental retardation and abnormal retinal synaptic transmission in DMD. Using immunohistochemistry, we find that alpha- and beta-DG are expressed in the outer plexiform layer of both wild type and mdx retina, where both dystrophin and dystrophin-related protein (DRP), but not laminin are present. In situ hybridization identifies two neuronal populations, photoreceptors and retinal ganglion cells, that express DG mRNA. Alpha- and beta-DG are also expressed in the inner limiting membrane and around blood vessels where they colocalize with laminin and DRP. Western blot analysis revealed the expression of several dystrophin isoforms in wild type and mdx retina, possibly explaining the unaltered expression of alpha- and beta-dystroglycan in the mdx central nervous system (CNS). Our results support the hypothesis that alpha- and beta-DG can interact with dystrophin and DRP in the CNS and perform functions analogous to those of the DGC in muscle.
Montanaro
F
F
Department of Biology, McGill University, Montreal, Canada.
Carbonetto
S
S
Campbell
K P
KP
Lindenbaum
M
M
D000818:Animals; D000918:Antibody Specificity; D015152:Blotting, Northern; D015153:Blotting, Western; D002490:Central Nervous System / Q000737:chemistry / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D049030:Dystroglycans; D016189:Dystrophin / Q000235:genetics* / Q000276:immunology / Q000648:ultrastructure; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007536:Isomerism; D007797:Laminin / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D012333:RNA, Messenger / Q000032:analysis; D012160:Retina / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D049411:Utrophin
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D007797:Laminin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C483600:Utrn protein, mouse; D049411:Utrophin; D049030:Dystroglycans