TABLE 1.

Current mouse models of Gars/CMT2D.

Mutation	Method of mutagenesis	Severity	Original publication
C201R	ENU-induced	Mild	Achilli et al., Dis Model Mech., 2009
ΔETAQ	CRISPR knock-in	Severe	Morelli et al., J Clin Invest., 2018
P278KY	Spontaneous	Severe	Seburn et al., Neuron, 2006
G240R	Adenovirus overexpression	Moderate	Seo et al., J Mol Histol., 2014
L129P	Adenovirus overexpression	Pain	Seo et al., J Korean Med Soc., 2014

Table 1 The C201R allele is not found in patients. While it causes marked weakness and reduced nerve conduction velocity, it has very little axon loss in motor or sensory nerves. The ΔETAQ allele is a mouse model recreating a de novo human mutation. It has a severe phenotype and pronounced axon loss in motor and sensory axons beginning at a few weeks of age. The P278KY allele is also not found in patients. It has a phenotype slightly more severe than ΔETAQ and can lead to premature mortality in an inbred genetic background. All three mutations are dominant and lead to a similar activation of the integrated stress response. The G240R and L129P mouse models were generated by viral overexpression of the mutant proteins. This has the advantage of efficiently testing pathogenicity for potential gain-of-function or dominant-negative alleles, but axonopathy was not characterized in these models.