Fig. 2

Neurodegeneration in cultured neurons transfected with ALS-associated SARM1 variants. (A) Neuron death as measured by the MTT assay and (B) axon degeneration as measured by Annexin V staining in Sarm1^−/− DRG neurons infected with lentivirus expressing SARM1 variant constructs as well as double mutant constructs including E642A, a point mutation that disrupts SARM1 NAD⁺ hydrolase activity, relative to the common SARM1 reference allele. All data are expressed as the percent of surviving cells or area of Annexin stained axons relative to neurons infected with the reference allele. (C) Representative bright-field and Annexin V-stained images of axons from Sarm1^−/− DRG cultures infected with variant and SARM1 reference allele constructs. *p < 0.005 difference from reference allele. These results demonstrate that constitutive SARM1 activity causes cell death and axon degeneration while expression of control SARM1 does not