title: Loss of short dystrophin isoform Dp71 in olfactory ensheathing cells causes vomeronasal nerve defasciculation in mouse olfactory system.
abstract: The Duchenne muscular dystrophy (DMD) gene encodes dystrophin, which is a protein defective in DMD patients, as well as a number of shorter isoforms, which have been shown to be expressed in various non-muscle, primarily neural, tissues. As of yet, the physiological function of the various dystrophin isoforms is not fully understood. In the present study, we investigated the neurological phenotype that arises in the DMD-null mice, where expression of all dystrophin isoforms had been disrupted. We demonstrate that vomeronasal axons in the DMD-null mice are defasciculated, and some of the defasciculated vomeronasal axons aberrantly entered into the main olfactory bulb, which indicates that the product(s) of the DMD gene plays an important role in vomeronasal nerve organization. Through western blot and immunofluorescence analyses, we determined that the dystrophin isoform Dp71 was exclusively expressed in the mouse olfactory system: mainly in the olfactory ensheathing cells (OECs), an olfactory system-specific glia cell that ensheaths fascicles of the olfactory nerve. In the OECs, Dp71 was co-localized with beta-dystroglycan, utrophin, laminin, and perlecan. Since beta-dystroglycan and perlecan expression was decreased in the OECs of DMD-null mice, we hypothesize that Dp71 expressed in the OECs participates in fasciculation of the vomeronasal nerve, most likely through interactions with extracellular matrix.
authors.affiliation: Laboratory of Molecular Embryology, Department of Bioscience, Kitasato University School of Science, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Takatoh
authors.forename: Hiroe
authors.initials: H
authors.lastname: Kudoh
authors.forename: Shunzo
authors.initials: S
authors.lastname: Kondo
authors.forename: Kazunori
authors.initials: K
authors.lastname: Hanaoka
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D049030:Dystroglycans / Q000378:metabolism; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D019147:Vomeronasal Organ / Q000002:abnormalities / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D016189:Dystrophin; D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; C085339:apo-dystrophin 1; C071927:perlecan; D049030:Dystroglycans