[An animal model of leukemogenesis using transgenic mice]

The bcr/abl chimeric oncoprotein is considered to be implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. To investigate its biological function and the role in leukemogenesis in vivo, we generated transgenic mice expressing p210bcr/abl driven by the metallothionein promoter. Two of six founder mice and the transgenic progeny of one leukemic founder mouse developed leukemias several months after birth. Phenotypically, each leukemic mouse showed a thymic enlargement, a marked splenomegaly, and/or lymphnode swellings. Pathological examination revealed that leukemic cells were infiltrated in all tissues examined, especially in thymus, spleen, liver, and lymphnode. Expression of the p210bcr/abl transgene product and increased phosphorylation of cellular proteins in leukemic tissues were detected by the Western blot analysis. In addition, the expressed p210bcr/abl protein was demonstrated to possess an enhanced kinase activity by the in vitro immunecomplex kinase assay. These results indicate that hematopoietic precursor cells expressing the p210bcr/abl transgene product acquired a proliferative advantage and eventually developed leukemias in transgenic mice. The p210bcr/abl transgenic mice are considered to be an excellent animal model to investigate p210bcr/abl function and its role in leukemogenesis in vivo.