Development of HTLV-I Tax transgenic mice as an animal model for adult T-cell leukemia by using T cell specific gene promoter.

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Human T-cell leukemia virus type I (HTLV-I) is a causative agent that induces adult T-cell leukemia/lymphoma (ATL). To investigate the therapeutic agent for ATL, it is necessary to establish an animal model. The HTLV-I regulatory protein Tax has been postulated to lead to the proliferation and transformation of T-cells in ATL. In this study, we attempted to develop transgenic (Tg) mice expressing HTLV-I Tax preferentially in T-cells under the control of a distal or proximal lck promoter that direct high expression in mature or immature T-cells, respectively. Tumors developed on the liver and lung of proximal-Tax #15, and on the liver, spleen and lung of distal-Tax #6. These tumors were not derived from T-cells. Histological examination of kidneys in proximal-Tax #15 and #16, distal-Tax #6 and #7 showed glomerular nephritis, whereas the nontransgenic mice had no lesion. No transgenic progeny were obtained from these founder mice. Therefore, offspring with Tax gene was obtained using in vivo fertilization technique in proximal-Tax Tg mice, and the change of genetic background of distal-Tax Tg mice from C57BL/6 to BDF1 produced offspring with Tax gene. Pathological and molecular biological analyses of these mice are in progress at our laboratory.