Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D 
(CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl 
tRNA synthetase (GlyRS). Here we report a dominant mutation in Gars that causes 
neuropathy in the mouse. Importantly, both sensory and motor axons are affected, 
and the dominant phenotype is not caused by a loss of the GlyRS aminoacylation 
function. Mutant mice have abnormal neuromuscular junction morphology and 
impaired transmission, reduced nerve conduction velocities, and a loss of 
large-diameter peripheral axons, without defects in myelination. The mutant 
GlyRS enzyme retains aminoacylation activity, and a loss-of-function allele, 
generated by a gene-trap insertion, shows no dominant phenotype in mice. These 
results indicate that the CMT2D phenotype is caused not by reduction of the 
canonical GlyRS activity and insufficiencies in protein synthesis, but instead 
by novel pathogenic roles for the mutant GlyRS that specifically affect 
peripheral neurons.