AAV9-Tert treatment improves blood counts in mice with short telomeres resulting from specific Tert deletion in the bone marrow. (A) Experimental design. G3 Tert^−/− mice with short telomeres were generated by consecutive crosses of Tert-deficient mice. Bone marrow from these G3 mice was isolated and transplanted into irradiated wild-type mice. After engraftment, mice were injected with AAV9-Tert or AAV9-empty virus particles. (B) HT-Q-FISH analysis of telomere length in PBMCs from wild-type, G1 Tert^−/−, and G3 Tert^−/− mice reveals progressive telomere shortening with consecutive mouse generations. (C) Kaplan-Meier survival curves show that AAV9-Tert treatment improves survival of mice with very short telomeres in the bone marrow due to Tert deficiency specifically in the bone marrow (irradiated wild-type mice transplanted with G3 Tert^−/− bone marrow). AAV9-Tert compared with AAV9-empty treatment improves erythrocyte counts (D), hemoglobin levels (E), platelet counts (F), and leukocyte counts (G). In all graphs, n indicates number of mice. Data are mean ± SEM. Statistical analysis: log-rank test in panel A; 2-sided Student t test in panels B and E-H; P values are shown.