Figure 1: Plasma cell neoplasms observed in the Mef^−/−Rad50^s/s mice.

(a) Kaplan-Meier curves showing the survival of wild type control, Mef^−/−, Rad50^s/s, and Mef^−/−Rad50^s/s mice. Mouse number of each group is demonstrated. (b) Macroscopic pathological findings of a representative 1-year-old Mef^−/−Rad50^s/s mouse and circulating plasma cells observed in Mef^−/−Rad50^s/s mice in the upper panels. Spleen weight (mg), hemoglobin concentration (g/dL), and frequency of circulating plasma cells in peripheral blood (%) were analyzed in 300–350-day-old wild type, Mef^−/−, and Mef^−/−Rad50^s/s mice in the lower panel. P values between wild type and Mef^−/−Rad50^s/s mice, and Mef^−/− and Mef^−/−Rad50^s/s mice are shown in each graph. (c) Histological images of tumor, spleen and bone marrow in a representative 1-year-old Mef^−/−Rad50^s/s mouse stained with hematoxylin and eosin at x400 magnification. (d) Immunohistochemical staining of the wild type and Mef^−/−Rad50^s/s spleens, using anti-CD138, anti-λ, and anti-κ antibodies. (e) Flow cytometric analysis of various tissues from 1-year-old Mef^−/−Rad50^s/s mice and age-matched wild type control mice. The profile of B220 and CD138 expression is shown. The number shows the frequency of each quadrant. (f) PCR detection of immunoglobulin gene rearrangements in tumor and normal spleen samples using V_H family-specific forward primers and a reverse primer at J_H4 to amplify variable-joining (V_H-J_H) regions of the IgH locus. An independent PCR assay amplifying a region of the GAPDH gene was performed for input control. A clear shift from multi-bands to mono-band can be observed in tumors only on the V_HJ568 amplification, suggesting the monoclonality of the tumor. SP: spleen control from wild type mice; T1, T2: tumor from Mef^−/−Rad50^s/s mice. (g) Cause of death in Mef^−/−Rad50^s/s mice, as determined by pathology, immunohistochemistry, and flow cytometry.