A transgenic mouse model of human T cell leukemia virus type 1-associated diseases

Takeo Ohsugi

doi:10.3389/fmicb.2013.00049

Abstract

Human T cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia/lymphoma (ATLL) and several inflammatory diseases. Tax, the protein encoded by HTLV-1, may be responsible for the development of the diseases caused by this virus. To investigate the pathogenic role of Tax, several transgenic mouse strains expressing Tax have been developed in recent years. These mice develop various tumors including large granular lymphocytic leukemia, as well as inflammatory diseases such as arthritis. These results suggest that Tax expression alone is sufficient to cause both malignant neoplastic diseases and inflammatory diseases. However, until recently, there were no tax transgenic mice that develop T cell leukemia and lymphoma resembling ATLL. The first successful induction of leukemia in T cells was pre-T cell leukemia generated in transgenic mice in which a mouse lymphocyte-specific protein tyrosine kinase p56lck (lck)-proximal promoter was used to express the tax gene in immature T cells. Subsequently, transgenic mice were established in which the lck-distal promoter was used to express Tax in mature T cells; these mice developed mature T cell leukemia and lymphoma that more closely resembled ATLL than did earlier mouse models.

Highlights

Human T cell leukemia virus type 1 (HTLV-1) was the first human retrovirus to be isolated (Poiesz et al, 1980)
It is estimated that 10–20 million people worldwide are infected with HTLV-1, which is endemic in southwestern Japan, the Caribbean Islands, South America, and Africa
Infection with HTLV-1 can result in an aggressive malignancy known as adult T cell leukemia/lymphoma (ATLL) or in inflammatory diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), after a prolonged period of latency often lasting between 20 and 50 years (Watanabe, 1997)

Summary

Takeo Ohsugi*

To investigate the pathogenic role of Tax, several transgenic mouse strains expressing Tax have been developed in recent years. These mice develop various tumors including large granular lymphocytic leukemia, as well as inflammatory diseases such as arthritis. These results suggest that Tax expression alone is sufficient to cause both malignant neoplastic diseases and inflammatory diseases. Transgenic mice were established in which the lck -distal promoter was used to expressTax in matureT cells; these mice developed mature T cell leukemia and lymphoma that more closely resembled ATLL than did earlier mouse models

INTRODUCTION

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CONCLUSION