[Development of thymic tumor in HTLV-I transgenic rats under control of a lymphoid tissue specific promoter]

The p40tax protein of Human T lymphocyte virus type I (HTLV-I) is known to be a transactivator not only for the own viral gene but also for the various cellular genes (host genes), including a number of cytokine genes and genes for cell proliferation. Its tumorigenicity was also reported in vivo, such as developments of mesenchymal tumor, neurofibroma, mammary carcinoma and large granular lymphocytic leukemia, using the transgenic technique. To investigate the tumorigenicity in lymphoid tissues, a series of HTLV-I pX transgenic rats (lck-pX rats) which expressed the pX gene under control of lymphocyte specific protein tyrosine kinase (p56 lck) gene type 1 promoter was produced. In some lines of lck-pX rats, pX mRNA was expressed selectively in the thymus, lymph nodes and spleen as expected. However, pX mRNA expression was also detected in other tissues from other lines of lck-pX rats. Thymic tumor with epithelial markers developed in lck-pX rats as early as 8 weeks of age and high expression of pX mRNA was detected in the tumor tissue. This is the demonstration that HTLV-I pX gene causes thymic tumor in the transgenic rat and an lck-pX rat may be a suitable animal model for elucidating pathogenetic role of HTLV-I pX gene in lymphoid tissue neoplasia.