CD45:Cre^+/−Pten^f/f develop lethal disease that affects lymphoid organs. (A-B) Kaplan-Meier curve of females and males analyzed for 60 weeks. Note that survival dramatically decreases after 20 weeks. (C) Macroscopic comparison of representative spleen, liver, thymus, and lymph nodes from CD45:Cre^+/−Pten^f/f (ko, left) and CD45:Cre^−/−Pten^f/f (wt, right). (D) Western blot from wt and ko spleens showing Cre recombinase expression, correlating with Pten loss and increased Akt phosphorylation (p-Akt), cyclin D1, and c-Myc levels. Membranes were reprobed with tubulin to ensure protein loading. (E) Representative images (×63) showing Papanicolau staining of blood extensions from CD45:Cre^−/−Pten^f/f and CD45:Cre^+/−Pten^f/f mice. (F) Representative images (×10) showing hematoxylin and eosin (H&E) staining and Pten and Ki-67 immunohistochemistry of spleens from CD45:Cre^−/−Pten^f/f and CD45:Cre^+/−Pten^f/f mice. (G-H) Quantification of mitotic activity and proliferation in spleens from CD45:Cre^−/−Pten^f/f and CD45:Cre^+/−Pten^f/f mice. Results are expressed as number of mitotic figures observed per 50 high-power microscope fields (G) and percent of total cells displaying nuclear staining for Ki-67 (H). Data are means ± standard deviation; **P ≤ .001; ***P ≤ .0001.