A new GARS mutation, S625L, sensitizes peripheral neurons to degeneration.

Document Type


Publication Date

Spring 2017

JAX Location

In: Student Reports, Summer 2017, Jackson Laboratory


Charcot-Marie-Tooth Disease (CMT) is a group of genetic and phenotypic diseases that affect the peripheral nervous system and has a global frequency of 1 in 2500 people. CMT can be categorized into many subtypes based on the involvement of the motor versus the sensory neurons, and the gene involved. Dominant mutation in Gars cause CMT Type 2D (CMT2D), which is characterized by slow degeneration of the neurons in the distal extremities where motor neurons are affected more than sensory neurons. The purpose of this study was to determine if the GarsS625L1+ mutation, the mouse homologue to the human S635L mutation sometimes found in CMT2D patients, sensitized peripheral nerves to degeneration leading to the development of CMT -like symptoms in mice. For this purpose, a GarsS625L1+, GarsS625L1C20IR, and GarsC201Rl+ mice were analyzed for neuropathy at four months of age. The GarsS625L1C201R mutant are similar to a compound heterozygous patient with two Gars mutation (S635L1R596Q). After performing standard protocols for assessing neuropathy, we found a significant neuropathy in our compound heterozygous GarsS625L1C201R mice suggesting that the GarsS625L1+ mutation sensitizes peripheral nerves to degeneration.

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