GARS1 and Charcot-Marie-Tooth disease: For example, the Pro to Lys-Tyr mutation (P278KY) in the GarsNsf249/+ mouse model of CMT2D did not exhibit reduced synthetase activity, and furthermore, heterozygous mice with a single null loss-of-function GARS allele exhibited reduced synthetase activity but none of the symptoms of CMT (Seburn et al, 2006).