Nudt15 deficiency caused accelerated weight loss and early death resulting from toxicity during thiopurine therapy in mice.Nudt15^−/− or wild-type mice received MP therapy (20, 5, or 1 mg/kg per day via IP injection) and monitored daily for weight loss (A) and survival (B). Across all dosage levels (red, brown, and green for 20, 5, and 1 mg/kg per day, respectively), weight loss was significantly more severe and precipitous in Nudt15^−/− mice compared with wild-type mice (indicated by dashed vs solid lines, respectively), leading to significantly earlier death resulting from toxicity in the former. In panel A, each line represents the mean percent weight loss relative to baseline, and the shade of the same color indicates standard deviation within the respective group.