RT Journal Article
SR Electronic
T1 The <em>Wld</em><sup><em>s</em></sup> Mutation Delays Robust Loss of Motor and Sensory Axons in a Genetic Model for Myelin-Related Axonopathy
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2833
OP 2839
DO 10.1523/JNEUROSCI.23-07-02833.2003
VO 23
IS 7
A1 Samsam, Mohtashem
A1 Mi, Weiqian
A1 Wessig, Carsten
A1 Zielasek, Jürgen
A1 Toyka, Klaus V.
A1 Coleman, Michael P.
A1 Martini, Rudolf
YR 2003
UL http://www.jneurosci.org/content/23/7/2833.abstract
AB 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/Wldstypically 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 Wlds 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 Wldsgene would be a promising approach to delaying detrimental axonal loss in myelin disorders.