AAV9-Tert treatment rescues the aplastic anemia phenotype in Trf1^lox/lox mice. (A) Experimental design. Mice were lethally irradiated and transplanted the following day with Trf1^lox/loxMx1-Cre bone marrow. After engraftment, Cre expression and Trf1 excision was induced by pI:pC injections for 5 weeks. One week later, mice were injected with AAV9-Tert or AAV9-empty particles. (B) Kaplan-Meier survival curves showing that AAV9-Tert treatment significantly rescues mouse survival. (C) Kaplan-Meier survival curves considering only those animals that died of aplastic anemia within 100 days after virus treatment show significant protection of AAV9-Tert treatment from deaths due to aplastic anemia. Platelet counts (D) and hemoglobin levels (E) in mice of the AAV9-Tert-treated and AAV9-empty-treated groups showing clear signs of anemia compared with healthy mice from the same AAV9-Tert-treated and AAV9-empty-treated groups. (F) Representative bone marrow images of healthy controls (no Cre-mediated induction of Trf1 deletion) and of mice with bone marrow aplasia. Genotypes and AAV9 treatments are indicated. Bars represent 500 μm (left) and 20 μm (right); hematoxylin and eosin stain. (G) Quantification of bone marrow cellularity expressed as number of nucleated cells per field. Four to 5 fields per mouse were counted. (H) Quantification of bone marrow cellularity expressed as the percentage of nuclear area (purple stain) to total areas per field. Four to 5 fields per mouse were counted. In all graphs, n indicates number of mice. Data are mean ± SEM. Statistical analysis: log-rank test in panels B and C; 2-sided Student t test in panels D, E, G, and H; P values are shown. n.s., not significant.