Delayed clinical onset in male mutant SOD1 transgenic mice deficient in the RAG2 gene. (A) Disease progression was significantly delayed in mSOD1/RAG2-/- mice (filled circles; n = 11) compared with mSOD1/RAG2+/+ mice (open circles; n = 13). (B) Kaplan Meier curve for symptomatic onset in mSOD1/RAG2+/+ mice (n = 13) and mSOD1/RAG2-/- mice (n = 11). Mice were evaluated for signs of motor deficiency with the following 4-point scoring system: 4 points, normal (no sign of motor dysfunction); 3 points, hind limb tremors were evident when suspended by the tail; 2 points, gait abnormalities were present; 1 point, dragging of at least one hind limb; 0 points, inability to right self within 30 s. We defined the point when the clinical score became 3 as being clinical onset. The mSOD1/RAG2-/- mice exhibited the disease phenotype at a later stage than the mSOD1/RAG2+/+ mice. (C) Time course of motor performance in the hanging-wire test. mSOD1/RAG2-/- mice (n = 11) performed significantly better than mSOD1/RAG2+/+ mice (n = 13). (D) Changes in mean body weight of mSOD1/RAG2-/- mice (n = 11) and mSOD1/RAG2+/+ mice (n = 13). (E) Kaplan-Meier survival curve. Absence of T and B cells did not affect the survival of mSOD1 mice (mSOD1/RAG2+/+ mice; n = 13, mSOD1/RAG2-/- mice; n = 11) (p = 0.13). Data are expressed as the mean ± SEM. Statistical analysis was done using the generalized Wilcoxon test for Kaplan-Meier curves (B,E) and a two-way repeated multivariate ANOVA (A, C, D) during 12 to 16 weeks of age. *:p < 0.05, #:p < 0.005.