Thymic atrophy characteristic in transgenic mice that harbor pX genes of human T-cell leukemia virus type I.

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Y Furuta, S Aizawa, Y Suda, Y Ikawa, H Kishimoto, Y Asano, T Tada, A Hikikoshi, M Yoshida, M Seiki

Author Information

Y Furuta: Laboratory of Molecular Oncology, Tsukuba Life Science Center, Physical and Chemical Institute (RIKEN), Ibaraki, Japan.

PMID: 2724422 DOI: 10.1128/JVI.63.7.3185-3189.1989

The human T-cell leukemia viruses (HTLV) are associated with T-cell malignancies in humans. The malignant transformation occurs after a long latency in some carriers, and its mechanism appears to be distinct from that of other classes of retroviruses which induce transformation through viral or cellular oncogenes. A widely postulated explanation is that the products of novel pX genes transactivate endogenous cellular genes which lead to tumor development in T cells. To directly examine the pathological effects of pX genes in vivo, we produced transgenic mice harboring the HTLV type I pX genes under several regulatory units: HTLV type I long terminal repeat, immunoglobulin enhancer-simian virus 40 promoter, and mouse mammary tumor virus long terminal repeat. Atrophy of the thymus was characteristic in these mice no matter which regulatory unit directed the expression of the genes.

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Animals

Atrophy

Cell Transformation, Neoplastic

Genes, Viral

Human T-lymphotropic virus 1

Mice

Mice, Transgenic

Thymus Gland

Thymus Neoplasms

Journal Article

Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I.Role of human T-cell leukemia virus type 1 X region proteins in immortalization of primary human lymphocytes in culture.In vivo expression of the HBZ gene of HTLV-1 correlates with proviral load, inflammatory markers and disease severity in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP).Human T-cell leukemia virus infection of human hematopoietic progenitor cells: maintenance of virus infection during differentiation in vitro and in vivo.Distinct regions in human T-cell lymphotropic virus type I tax mediate interactions with activator protein CREB and basal transcription factors.Augmentation of c-fos and c-jun expression in transgenic mice carrying the human T-cell leukemia virus type-I tax gene.Targeting HTLV-1 activation of NFκB in mouse models and ATLL patients.From Immunodeficiency to Humanization: The Contribution of Mouse Models to Explore HTLV-1 Leukemogenesis.Mouse models of human T lymphotropic virus type-1-associated adult T-cell leukemia/lymphoma.Mouse Models for HTLV-1 Infection and Adult T Cell Leukemia.

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