biostudies-literatureGilley JMedical Research CouncilMotor Neurone Disease AssociationBiotechnology and Biological Sciences Research Council10-16https://www.ebi.ac.uk/biostudies/studies/S-EPMC5640801biostudies-literatureUnknown21(1)Studies with the Wld^S mutant mouse have shown that axon and synapse pathology in several models of neurodegenerative diseases are mechanistically related to injury-induced axon degeneration (Wallerian degeneration). Crucially, an absence of SARM1 delays Wallerian degeneration as robustly as Wld^S, but their relative capacities to confer long-term protection against related, non-injury axonopathy and/or synaptopathy have not been directly compared. While Sarm1 deletion or Wld^S can rescue perinatal lethality and widespread Wallerian-like axonopathy in young NMNAT2-deficient mice, we report that an absence of SARM1 enables these mice to survive into old age with no overt phenotype, whereas those rescued by Wld^S invariantly develop a progressive neuroCell reportsSarm1 Deletion, but Not Wld^S, Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy.PMC5640801RIBCHESTER/APR15/838-791BBS/E/B/000C0433MR/M024075/1MR/N004582/1G1000702Ribchester RRColeman MPGilley JfalseSarm1 Deletion, but Not Wld^S, Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy.Studies with the Wld^S mutant mouse have shown that axon and synapse pathology in several models of neurodegenerative diseases are mechanistically related to injury-induced axon degeneration (Wallerian degeneration). Crucially, an absence of SARM1 delays Wallerian degeneration as robustly as Wld^S, but their relative capacities to confer long-term protection against related, non-injury axonopathy and/or synaptopathy have not been directly compared. While Sarm1 deletion or Wld^S can rescue perinatal lethality and widespread Wallerian-like axonopathy in young NMNAT2-deficient mice, we report that an absence of SARM1 enables these mice to survive into old age with no overt phenotype, whereas those rescued by Wld^S invariantly develop a progressive neuro2017-01-01T00:00:00Z2017 Oct2025-04-22T21:15:59.961Z2019-03-27T02:58:58ZS-EPMC56408012897846510.1016/j.celrep.2017.09.027