Fig. 10
Increased TGM2 activity contributes to the onset and severity of ataxia in Smox/Sat1-dKO mice. a Activity of TGM2 was compared in Wt, Wt + Cys, Smox/Sat1-dKO and Smox/Sat1-dKO + Cys mice (n = 3/genotype, samples were assayed in triplicate, t = 3/sample). The TGM2 activity was significantly higher in both Smox/Sat1-dKO and Smox/Sat1-dKO + Cys compared to Wt mice (p = 8.15 × 10−6 and p = 0.00017 respectively). The Cys-treated Smox/Sat1-dKO mice also had significantly lower cerebellar TGM2 activity compared to untreated Smox/Sat1-dKO mice (p = 0.000044). Each unit of TGM2 activity is defined as “the amount of TGM2 that catalyzes the formation of μmole of hydroxyamate per minute from z-Gln-Gly-OH and hydroxylamine at pH 6.0 at 37 °C.” b Comparison of CAS of Wt, Wt + Cys, Smox/Sat1-dKO, and Smox/Sat1-dKO + Cys (n = 6/genotype). The CAS of Cys-treated Smox/Sat1-dKO mice in weeks 12 (p = 0.0029), 14 (p = 0.0304), and 16 (p = 0.0262) were significantly improved compared to untreated Smox/Sat1-dKO mice. c Comparison of rotarod latency of fall in Wt, Wt + Cys, Smox/Sat1-dKO, and Smox/Sat1-dKO + Cys mice (n = 6/genotype). The inhibition of TGM activity significantly improved the rotorod performance of Smox/Sat1-dKO mice in weeks 10 (p = 0.0119), 12 (p = 0.000022), 14 (p = 0.0015), and 16 (p = 0.002) compared to age-matched untreated Smox/Sat1-dKO mice. (*) Denotes p < 0.05, (**) denotes p < 0.01 for comparisons between Wt, Wt + Cys, Smox/Sat1-dKO, and Wt. (+) Denotes p < 0.05 and (++) denotes p < 0.01 for comparison between Wt and Smox/Sat1-dKO + Cys mice. (#) Denotes p < 0.05 for comparisons between Smox/Sat1-dKO and Smox/Sat1-dKO + Cys mice