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HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)-like disease and toxic epidermal necrolysis (TEN)-like disease in HTLV-1 Tax transgenic mice

Human T-cell leukemia virus type 1 (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATLL), as well as inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We created a transgenic mouse model of HTLV-1 infection by using the distal promoter of Lck to express tax in mature thymocytes and peripheral T lymphocytes. Major phenotypes of disease in this model were mature T cell leukemia/lymphoma similar to ATLL and an inflammatory arthropathy. While expanding the transgenic mouse colony, we also found 2.7% of transgenic mice developed a HAM/TSP-like disease and 2.4% of transgenic mice developed a toxic epidermal necrolysis (TEN)-like disease. The HAM/TSP-like disease with symmetrical paraparesis of the hind limbs in transgenic mice was not inflammatory, unlike that found in HAM/TSP patients, but instead involved the invasion of histiocytic sarcoma cells into the lumbar spinal cord from the bone marrow where they had undergone extensive proliferation. Mice with the HAM/TSP-like disease showed abnormal expression of cytokines and chemokines, including TNF and IL-6. There are no reports of spontaneous symmetrical paraparesis caused by histiocytic sarcoma in mice. TEN is characterized by a rash, bullae, and diffuse exfoliation of wide cutaneous surface areas, as seen in second-degree burns. Massive keratinocyte apoptosis is the hallmark of TEN. The TEN-like disease in transgenic mice occurred mainly in C57BL/6 background strain mice. These mice showed a skin detachment rate of greater than 30%. The pathology in transgenic mice with a TEN-like disease is currently under study and will be discussed.

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Correspondence to Takeo Ohsugi.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Ohsugi, T., Wakamiya, M., Morikawa, S. et al. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)-like disease and toxic epidermal necrolysis (TEN)-like disease in HTLV-1 Tax transgenic mice. Retrovirology 11 (Suppl 1), P40 (2014).

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