Polg^A mice develop age-related macrocytic anemia and leukopenia associated with dysfunction of mitochondria isolated from both liver and spleen. (A-D) Peripheral-blood samples from both Polg⁺ and Polg^A mice were analyzed from 2 to 17 months of age. Each point represents the mean ± SEM of Polg⁺ mice (n = 3-12, solid lines) and Polg^A mice (n = 3-9, dotted lines). (A) Hemoglobin levels. (B) Mean corpuscular volume of all RBCs (□) and of reticulocytes only (◇). (C) Platelet count. (D) White blood cell (WBC) count. (E) Representative Wright-Giemsa–stained images of RBCs and lymphocytes from peripheral-blood smears of 15-month-old mice. Bars represent 10 microns. (F) The relative activity of the mtDNA-dependent mitochondrial enzyme cytochrome c oxidase (COX) was compared with that of the nuclear DNA-dependent mitochondrial enzyme citrate synthase (CS) in mitochondria isolated from the livers and spleens of both Polg⁺ and Polg^A mice at the indicated ages. Each bar represents the mean ± SEM of mitochondria isolated from liver or spleen, respectively, of Polg⁺ mice (n = 3-6, cross-hatched) and Polg^A mice (n = 3-5, gray) at the indicated age. *P < .05 (statistical significance) by Student t test; **P < .01