An HTLV-I Transgenic Mouse Model: Role of the Tax Gene in Pathogenesis in Multiple Organ Systems
The human T-lymphotropic virus type I (HTLV-I) has been associated with a lymphoproliferative disease called adult T-cell leukemia/lymphoma (ATLL) (Poiesz et al. 1980; Yoshida et al. 1982; Hinuma et al. 1981; Kalyanaraman et al. 1982) and a neurodegenerative disease called tropical spastic paraparesis (TSP) (Gessain et al. 1985; Rodgers-Johnson et al. 1985; Bartholomew et al. 1986) or HTLV-I-associated myelopathy (HAM) (Osame et al. 1986a). These diseases appear to share few common clinical features. ATLL has a prolonged latency, but once established is frequently rapidly fatal (Broder et al. 1984). The disturbance consists of a monoclonal expansion of mature peripheral T cells each of which contains copies of retroviral sequences (Poiesz et al. 1980; Miyoshi et al. 1980; Yamamoto et al. 1981; Popovic et al. 1983; Chen et al. 1983; Yoshida et al. 1984). Death results from consequences of uncontrolled cellular proliferation and dysfunction. In contrast, the associated neurologic disease usually shows a shorter latency period and a slowly progressive course (Roman 1988; Osame et al. 1986a). Though variable degrees of HTLV-I-infected lymphocytic infiltration into the CNS may be seen in this disease, the cellular target for viral infection within the nervous system remains unclear (Jacobson et al. 1988). To study potential mechanisms of these disparate HTLV-I-induced diseases, we created a transgenic mouse model in which the tax gene (trans-activator of transcription) was introduced under control of the HTLV-I viral long-terminal repeat (LTR) promoter.
KeywordsLymphoma Leukemia Neurol NADH Acetyl
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