title: Impaired fast axonal transport in neurons of the sciatic nerves from dystonia musculorum mice.
abstract: Dystonia musculorum (dt) mice suffer from a severe sensory neuropathy caused by mutations in the gene encoding the cytoskeletal cross-linker protein dystonin/bullous pemphigoid antigen 1 (Bpag1). Loss of function of dystonin/Bpag1 within neurons leads to a loss in the maintenance of cytoskeletal organization and to the development of focal axonal swellings prior to death of the neuron. In the present study, we demonstrate that neurons within the sciatic nerves of dt27J mice undergo axonal degeneration as has been previously reported for the dorsal roots. Furthermore, ultrastructural studies reveal a perturbed organization of the neurofilament and microtubule networks within the axons of sciatic nerves in dt27J mice. The disrupted cytoskeletal organization suggested that axonal transport is affected in dt mice. To address this, we assessed fast axonal transport by measuring the rate of accumulation of acetylcholinesterase (AChE) proximal and distal to a surgically introduced ligature on the sciatic nerves of normal and dt27J mice. Our findings demonstrate that axonal transport of AChE in both orthograde and retrograde directions is markedly affected, and allow us to conclude that axonal transport defects do exist in the sciatic nerves of dt27J mice.
authors.affiliation: Ottawa Health Research Institute, Ottawa, Ontario, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: De Repentigny
authors.forename: Julie
authors.initials: J
authors.lastname: Deschênes-Furry
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Jasmin
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kothary
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D001369:Axons / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D001921:Brain / Q000201:enzymology; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics; D003599:Cytoskeleton / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D020821:Dystonic Disorders / Q000235:genetics / Q000503:physiopathology*; D000071821:Dystonin; D005727:Ganglia, Spinal / Q000201:enzymology; D008026:Ligation; D051379:Mice; D008818:Mice, Neurologic Mutants; D018482:Muscle, Skeletal / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D012584:Sciatic Nerve / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D013116:Spinal Cord / Q000201:enzymology
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C095667:Dst protein, mouse; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D000110:Acetylcholinesterase