3-NP-induced toxicity in wild-type and hMTH1-Tg^+/− and hMTH1-Tg^+/+ transgenic mice.

<p>Groups of wild-type (n = 20), <i>hMTH1-Tg^+/−</i> (n = 16) and <i>hMTH1-Tg^+/+</i> (n = 16) mice were injected i.p. twice daily for 5 days with 60 mg/kg 3-NP. Wild-type (black bars), <i>hMTH1-Tg^+/−</i> (grey bars) and <i>hMTH1-Tg^+/+</i> (white bars). (A) Weight loss. Body weight, measured immediately before the first injection on the indicated days, is expressed as a percentage of the pretreated body weight. (B) Motor impairment. Mice were monitored twice a day for dystonia and/or gait abnormalities. Neurological score was as follows: intermittent dystonia of one hindlimb: 1; intermittent dystonia of two hindlimbs: 2; permanent dystonia of hindimbs: 3; uncoordinated and wobbling gait or recumbency: 3; near death recumbency: 4. For each animal, the highest neurological score reached at any time of the observation period was considered. Values are mean±standard errors. (C) Cumulative mortality. The non-surviving fraction at the end of 5-day treatment is expressed as a percentage of starting total. (D) Striatal lesion formation. The percentage of animals with detectable post-mortem striatal lesions is shown. (E) Size of striatal lesions. Postmortem measurements of striatal lesions along the rostrocaudal axis. The asterisks indicate a P<0.05 <i>vs</i> wild-type according to One-way Anova and Tukey multiple comparison post-hoc test for panels A, B and E and to χ² test for panels C and D.