Sarm1 (K597E) is a potent dominant negative, blocking axon degeneration after axotomy. (A) Axons from WT DRG neurons expressing the indicated Sarm1 construct were transected, and the degeneration of distal axons monitored over time. Expression of Sarm1 (K597E) delays axon degeneration for ∼36 h postaxotomy. (B) Expression of SARM1 (K597E) also preserves axon integrity in response to the chemotherapeutic agent vincristine. Axons were treated with 40 nM vincristine, and axon degeneration was measured 36 h postexposure. Expression of SARM1 (K597E) suppresses axon degeneration (C) and cell death (D) in response to the mitochondrial uncoupling agent CCCP (50 μM, 24 h). *P < 0.05; **P < 0.01. Error bars reflect ± SEM (n = 3). (Scale bars, 25 μM.)