Figure 2.
Enforced hematopoietic expression of Snai1 predisposes mice to AML development. (A) Quantitative real-time PCR analysis showing Snai1 mRNA levels were approximately eightfold to 15-fold higher in transgenic mouse bone marrow, as compared with WT controls (Snai1+/+, n = 3; Snai1tg/+, n = 3; Snai1tg/tg, n = 3). Data are presented as mean + standard error of the mean. (B) Kaplan-Meier plot showing Snai1 transgenic mice become moribund from ∼12 months of age, with a median age of 601 days for Snai1tg/tg and 418 days for Snai1tg/+. No significant difference in survival was observed between heterozygous and homozygous transgenic mice. (C) Pictograph showing splenomegaly in an Snai1tg/tg mouse. (D) Representative flow cytometric plots with predominant CD11b+GR1+ cell populations in both the bone marrow and spleen. Flow cytometric profiles of CD11b and GR1 expression on bone marrow and spleen cells are shown for a representative WT mouse in the top panel, a moribund mouse with a myeloproliferative disease in the middle panel, and a mouse with AML in the bottom panel. (E) Hematoxylin and eosin staining of bone marrow, spleen, and peripheral blood histological sections of the same mice as in panel D are shown. A representative WT mouse is depicted in the top panel. A representative mouse with myeloproliferative disease is shown in the middle panel, with evidence of granulocytic cell infiltration in the spleen and blood, increased numbers of granulocytic precursor and mature cells in the bone marrow and spleen, and reduced erythropoiesis. In the bottom panel, a representative mouse with AML is shown as evidenced by myeloid blast cell infiltration into bone marrow, spleen, and peripheral blood, along with loss of normal hematopoiesis in the bone marrow and spleen. *P < .05 1-tailed Student unpaired t test, **P < .01 Mantel-Cox test.