Lymphoid-specific loss of MNT greatly diminishes lymphoma development and induces lymphopenia in Eμ-Myc mice. (A) Kaplan-Meier survival curves showing reduced lymphoma development in Mntfl/fl Eμ-Myc/Rag1Cre mice (blue; median survival, 463 days) than Mntfl/+ Eμ-Myc/Rag1Cre mice (lime green; median survival, 138 days) and control Eμ-Myc mice (red; median survival, 86 days) and Eμ-Myc/Rag1Cre mice (purple; median survival, 96 days). **P ≤ .01; ****P ≤ .0001. Log-rank test. Killed mice showing no malignancy on autopsy were censored (black mark). X-axis was arbitrarily terminated at 400 days, but monitoring continued. (B) PCR analysis shows efficient deletion of floxed Mnt alleles by Rag1Cre in cells sorted from bone marrow of individual 4-week-old mice. WT and floxed Mnt alleles both produce 147-bp fragments, deleted Mnt allele (MntΔ), a 386-bp fragment. Lanes 1,2: pro-B and pre-B cells, respectively, from Mntfl/fl Eμ-Myc/Rag1Cre mouse #360; lanes 3,4: pre-B cells from control Mnt+/+
Rag1Cre mice (#403, #404); lanes 5,6 pre-B cells from Mntfl/fl
Rag1Cre mice (#413, #414); C, control DNA for Mnt PCRs. (C-D) Lymphoid-specific MNT loss induces lymphopenia. Flow cytometric quantification of B lymphoid subpopulations in bone marrow (C) and spleen (D) of 4-week-old WT (light green), Eμ-Myc (red), Eμ-Myc/Rag1Cre (purple), and Mntfl/fl Eμ-Myc/Rag1Cre (blue) mice. Supplemental Figure 3A exemplifies sorting strategy. Bar graphs show mean ± SD; *P ≤ .05; **P ≤ .01; ***P ≤ .001; ****P ≤ .0001. (E) Lymphocyte count in blood of 4-week-old mice of indicated genotypes, determined in an Advia hematology analyzer. Mean ± SD; *P ≤ .05; **P ≤ .01; ***P ≤ .001; ****P ≤ .0001.