The Wlds mutation delays robust loss of motor and sensory axons in a genetic model for myelin-related axonopathy.
Mice deficient in the peripheral myelin component P0 mimic severe forms of inherited peripheral neuropathies in humans, with defective myelin formation and consequent axonal loss. We cross-bred these mice with the spontaneous mutant C57BL/Wld(s) typically showing protection from Wallerian degeneration because of fusion of the ubiquitination factor E4B (Ube4b) and nicotinamide mononucleotide adenylyltransferase (Nmnat) genes. We found that in the double mutants, the robust myelin-related axonal loss is reduced at 6 weeks and 3 months of age. Moreover, retrograde labeling from plantar nerves revealed an increased survival of motor axons. These motor axons appeared functionally active because both the amplitude of compound muscle action potentials and muscle strength were less reduced in the double mutants. At 6 months of age, reduction of axonal loss was no longer detectable in the double mutants when compared with littermates carrying the P0 null mutation only, although the Wld(s) gene was not reduced in its expression at this age. We conclude that myelin-related axonal loss is a process having some features in common with Wallerian degeneration. Introducing the Wld(s) gene would be a promising approach to delaying detrimental axonal loss in myelin disorders.
Samsam
Mohtashem
M
Department of Neurology, University of Würzburg, D-97080 Würzburg, Germany.
Mi
Weiqian
W
Wessig
Carsten
C
Zielasek
Jürgen
J
Toyka
Klaus V
KV
Coleman
Michael P
MP
Martini
Rudolf
R
D000200:Action Potentials; D000367:Age Factors; D000818:Animals; D001369:Axons / Q000473:pathology*; D003711:Demyelinating Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004553:Electric Conductivity; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008957:Models, Genetic; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D009154:Mutation; D018993:Myelin P0 Protein / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009475:Neurons, Afferent / Q000473:pathology / Q000502:physiology; D010525:Peripheral Nerves / Q000473:pathology; D014855:Wallerian Degeneration / Q000235:genetics
D018993:Myelin P0 Protein; D009419:Nerve Tissue Proteins; C442580:Wld protein, mouse