HPRT knockdown and 6TG treatment potently select for gene-modified hematopoietic progenitor cells in mice. Primary BM cells were harvested from donor mice, transduced with CtrlG and 491G vectors, and transplanted into recipient mice. Peripheral blood was periodically analyzed by flow cytometry. (A,B) The percentage of GFP⁺ cells within the Gr1⁺ (A) and B220⁺ (B) peripheral blood cell populations from recipients of 491G-transduced BM is plotted versus time. Note log scale. Five-day courses of treatment are indicated by □ (0.25 mg/kg per day), ■ (2 mg/kg per day), or (0.5 mg/kg per day). The number of 6TG-treated mice at weeks 14 and 16 in the high/moderate dosing experiment is 4 and 3, respectively, because of toxicity-related deaths. (C) Complete blood counts from mice in the low-dose experiment were performed at day 22 of cycle 2 (week 12). The hemoglobin concentration and absolute granulocyte counts (AGC) are depicted. AGC was calculated using the total white blood cell count multiplied by the fraction of Gr1⁺ cells as determined by flow cytometry. NS indicates not significant. (D) The weights of all PBS- and 6TG-treated mice were determined at day 22 of cycle 2 (week 12) in the low-dose experiment.