Development and characterization of a novel CD19CherryLuciferase (CD19CL) transgenic mouse for the preclinical study of B-cell lymphomas

Purpose: To generate a transgenic mouse that when crossed with spontaneous mouse models of lymphoma will allow for quantitative in vivo measurement of tumor burden over the entire spectrum of the disease and or response to therapy in a "disease" or lymphoma subtype-specific manner. Experimental Design: We developed a novel genetically engineered transgenic mouse using a Cherry-Luciferase fusion gene targeted to the CD19 locus to achieve B-cell-restricted fluorescent bioluminescent emission in transgenicmousemodels of livingmice. The use of a dual function protein enables one to link the in vivo analysis via bioluminescence imaging to cell discriminating ex vivo analyses via fluorescence emission. Results: The spatiotemporal tracking of B-cell lymphoma growth and the response of an established B-cell lymphoma to a drug known to induce remission was evaluated in a double transgenic animal obtained by crossing the CD19CherryLuciferase transgenic mouse to a mouse model of an aggressive B-cell lymphoma. The observations validated the use of the CD19CherryLuciferase transgenic mouse in the assessment of an active drug routinely used in the treatment of lymphoproliferative malignancies. Conclusions: The transgenic mouse described here is the first of its kind, intended to be used to hasten translational studies of novel agents in lymphoma, with the intent that understanding the relevant pharmacology before clinical study will accelerate successful development in clinical studies.