In Slit2 mutant mice, motor nerves prematurely defasciculate into smaller bundlers in various muscles, unlike those in wild type that stay in compact fascicle until they reach the middle of muscle fibers.
PTPBL-KO (non receptor like PTP-NRPTP) mice display impaired motor nerve repair in a model of sciatic nerve crush lesion [ 8] and PTPMEG (NRPTP) interacts with key intracellular players leading to the stimulation of the channel activity of NMDA receptors [ 9].
Of note, in contrast to isoform P1c knockout mice, a defect in motor nerve conduction velocity of sciatic nerve could not be detected in conditional, Schwann cell-specific plectin knockout (P0-Cre/cKO) mice (authors'unpublished data), suggesting that this phenotype is specifically related to axonal P1c.
Motor nerve stimulation-induced Pgc-1α and Vegf mRNA expression in TA muscle was significantly attenuated in p38γ MKO mice (Fig. 4A), whereas neither the motor nerve stimulation nor the p38γ gene deletion in skeletal muscle had significant impact on Pgc-1β mRNA expression.
Motor nerve terminals were imaged in all mice and EMG recorded in three of the mice for up to 60 min. Nerve terminal and postsynaptic endplate imaging using 4-Di-2-asp and Alexa488- α-BTX, respectively, were repeated in three rats.
We found a subset of genes with diminished or loss of induction upon motor nerve stimulation in p38γ MKO mice.
27, 36, 69 Thus, while Wallerian degeneration is complete within 1 3 days of axotomy in wild-type mice, almost all of the intramuscular axons and motor nerve terminals remain wholly intact for about 3 days after section of the sciatic nerve and only then degenerate, in a progressive fashion, via a process of asynchronous retraction of synaptic boutons from motor endplates.
Axons and motor nerve terminals were labeled with a mouse monoclonal antibody against the phosphorylated heavy fragment of neurofilament protein (SMI31, 1 400, Sternberger Monoclonal).
Comparison of wild-type and cIgf1r ko mice revealed that distal compound motor action potentials (CMAPs), motor nerve conduction velocities (M-NCVs) and compound sensory motor nerve conduction velocities (cSNCVs) were not significantly reduced in cIgf1r ko mice (P > 0.05, two-tailed Student's t test) (electronic supplementary Fig. A5).
In contrast, we found degeneration of phrenic motor nerve fibers and terminals in P5 DKO mice.
