EμSR-FGFR3 TDII transgenic mice develop a fatal pro–B-cell lymphoma. (A) Schematic diagram of EμSR-FGFR3 TDII transgenic construct. FGFR3 TDII cDNA was inserted following the 3′ of EμSR promoter/enhancer using a Gateway subcloning cassette. The 2 filled boxes flanking the FGFR3 TDII construct are Gateway recombination sequences. The open bar indicates the target fragment for Southern blot analysis. (B) Southern blot identification of 2 positive founders with EμSRFGFR3 TDII transgenic construct. Genomic tail DNA was digested with BglII, and the fragment containing FGFR3 TDII cDNA sequence was detected (indicated by an arrow). An FGFR3 TDII transgene-negative FVB founder tail DNA is shown as a control. (C) Gross analysis of affected EμSR-FGFR3 TDII transgenic founder A.5652 shows splenomegaly and massive lymphadenopathy in various lymph node (LN) groups as indicated. (D) Sections of tissues from mouse A.5652 demonstrate extensive infiltration and effacement by immature lymphoid cells in lymph node, spleen, and bone marrow and focally in the liver. Magnifications are as indicated (H&E). (E) Flow cytometry analysis of lymph nodes in mouse A.5652 illustrates an immunophenotype with a high percentage of pro–B lymphoid cells, identified as B220⁺, CD19⁺, CD25⁺, CD43⁺, and c-KIT⁺ but BP-1^-. Images were captured as described for Figure 4.