Genetic ablation of Sarm1 attenuates axonal degeneration in a mouse model of CMT2J

Sarm1 ablation partially reduces axonal degeneration in 12-month-old homozygous MpzT124M/T124M mice, lowering plasma neurofilament light chain and preserving peripheral nerve integrity.

• Why it matters: CMT2J from MPZ T124M shows progressive axonal loss, and SARM1 is a key executioner of programmed axonal degeneration, but its contribution in this model was unclear.
• What they did: MpzT124M mice were crossed with Sarm1-null animals, and electrophysiological, morphological, and molecular measures were compared in heterozygous and homozygous mutants.
• The result: Sarm1 deletion did not rescue electrophysiological deficits, but it partially reduced axonal degeneration in 12-month-old homozygous mutants and improved motor performance with reduced disease signs by 18 months in heterozygous MpzT124M/+ mice.