Alterations in myelination in the central nervous system of dystonia musculorum mice.
Dystonia musculorum (dt) is an autosomal recessive sensory neuropathy in mice resulting from a mutation in the gene encoding the cytoskeletal linker protein Bpag1. In addition to neurodegeneration, dt mice display myelination abnormalities in the peripheral nervous system. In this report we investigated whether myelination abnormalities are also present in the central nervous system of dt(Tg4) mice. Transcripts for both neural isoforms of Bpag1 (a1 and a2) were detected in optic nerves and spinal cords of wild-type mice. Light microscopy of resin-embedded thin sections revealed a reduction in myelinated axons in both optic nerves and spinal cords in dt(Tg4) mice. As well, hypermyelinated axons were detected in these tissues. Ultrastructural analysis of optic nerves and spinal cords from dt(Tg4) mice revealed an increase in the number of amyelinated axons, the presence of hypo- and hypermyelinated axons, and redundant myelin that course away from axons. Changes in the level of myelin proteins accompanied the morphological alterations. Myelin-associated glycoprotein levels were reduced in optic nerves of dt(Tg4) mice, and myelin basic protein levels were altered in optic nerves, sciatic nerves, and spinal cords of affected mice. Short-term cultures of oligodendrocytes derived from dt(Tg4) mice did not show morphological alterations.
Ottawa Health Research Institute and The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada.
Ron
R
Saulnier
Yves
Y
De Repentigny
Voon Wee
VW
Yong
Rashmi
R
Kothary
D000818:Animals; D001324:Autoantigens / Q000032:analysis*; D002352:Carrier Proteins; D018929:Cell Culture Techniques; D002490:Central Nervous System / Q000473:pathology* / Q000648:ultrastructure; D003094:Collagen / Q000032:analysis*; D003598:Cytoskeletal Proteins / Q000032:analysis*; D004422:Dystonia Musculorum Deformans / Q000235:genetics* / Q000473:pathology*; D000071821:Dystonin; D015151:Immunoblotting; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D004676:Myelin Basic Protein / Q000032:analysis; D009186:Myelin Sheath / Q000235:genetics* / Q000473:pathology*; D018992:Myelin-Associated Glycoprotein / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis*; D024041:Non-Fibrillar Collagens; D009836:Oligodendroglia / Q000473:pathology; D009900:Optic Nerve / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000473:pathology; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D004676:Myelin Basic Protein; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C095667:Dst protein, mouse