title: Targeted inactivation of dystrophin gene product Dp71: phenotypic impact in mouse retina.
abstract: The abnormal retinal neurotransmission observed in Duchenne muscular dystrophy (DMD) patients and in some genotypes of mice lacking dystrophin has been attributed to altered expression of short products of the dystrophin gene. We have investigated the potential role of Dp71, the most abundant C-terminal dystrophin gene product, in retinal electrophysiology. Comparison of the scotopic electroretinograms (ERG) between Dp71-null mice and wild-type (wt) littermates revealed a normal ERG in Dp71-null mice with no significant changes of the b-wave amplitude and kinetics. Analysis of DMD gene products, utrophin and dystrophin-associated proteins (DAPs), showed that Dp71 and utrophin were localized around the blood vessels, in the ganglion cell layer (GCL), and the inner limiting membrane (ILM). Dp71 deficiency was accompanied by an increased level of utrophin and decreased level of beta-dystroglycan localized in the ILM, without any apparent effect on the other DAPs. Dp71 deficiency was also associated with an impaired clustering of two Müller glial cell proteins-the inwardly rectifying potassium channel Kir4.1 and the water pore aquaporin 4 (AQP4). Immunostaining of both proteins decreased around blood vessels and in the ILM of Dp71-null mice, suggesting that Dp71 plays a role in the clustering and/or stabilization of the two proteins. AQP4 and Kir4.1 may also be involved in the regulation of the ischemic process. We found that a transient ischemia resulted in a greater damage in the GCL of mice lacking Dp71 than in wt mice. This finding points at a crucial role played by Dp71 in retinal function.
authors.affiliation: INSERM U-592, Laboratoire de Physiopathologie Cellulaire et Moléculaire de la Rétine, Hôpital Saint-Antoine, Bâtiment Kourilsky, 6ème étage, 184 rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Dalloz
authors.forename: Rachel
authors.initials: R
authors.lastname: Sarig
authors.forename: Patrice
authors.initials: P
authors.lastname: Fort
authors.forename: David
authors.initials: D
authors.lastname: Yaffe
authors.forename: Agnès
authors.initials: A
authors.lastname: Bordais
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.forename: Jens
authors.initials: J
authors.lastname: Grosche
authors.forename: Dominique
authors.initials: D
authors.lastname: Mornet
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: José
authors.initials: J
authors.lastname: Sahel
authors.forename: Uri
authors.initials: U
authors.lastname: Nudel
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rendon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049030:Dystroglycans; D016189:Dystrophin / Q000031:analogs & derivatives* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004594:Electrophysiology; D004596:Electroretinography; D005724:Ganglia / Q000378:metabolism; D005838:Genotype; D007150:Immunohistochemistry; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009457:Neuroglia / Q000378:metabolism; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D012160:Retina / Q000473:pathology* / Q000502:physiology; D049411:Utrophin
chemical_list: D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D024661:Potassium Channels, Inwardly Rectifying; C483600:Utrn protein, mouse; D049411:Utrophin; C085339:apo-dystrophin 1; D049030:Dystroglycans