アクティブボード・2008年 3月
     ・・・・・2008年 3月 2日更新・・・・・

研究発表を行った学会;
・13th International Conference on Human Retrovirology HTLV-I and Related Viruses、
 2007年5月21日~25日(箱根)

タイトル;Development T Cell Leukemia/Lymphoma and Arthropathy in Transgenic Mice Carrying Human T Cell Leukemia Virus Type 1 tax Gene.

発表者; 大杉 剛生 氏
   (熊本大学 生命資源研究・支援センター 病態遺伝分野)
Abstract;
Human T-cell leukemia virus type I (HTLV-I) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL). HTLV-I infection has also been linked with a broader spectrum of diseases, including myelopathy (HAM/TSP), uveitis, arthropathy and dermatitis. Tax protein encoded by the pX region in the HTLV-I may be responsible for the development of diseases caused by this virus. We have developed a transgenic mouse model of HTLV-I by using a mouse lymphocyte-specific protein-tyrosine kinase (Lck) distal promoter to express the tax gene in mature thymocytes and peripheral T lymphocytes. These mice developed T cell lymphoma/leukemia with marked splenomegaly, hepatomegaly and lymphadenopathy. Total white blood cell count was significantly elevated, large and abnormal leukemic cells comprised >80% of the peripheral blood mononuclear cells in blood smear. The clonal phenotype of the leukemic cells was CD4+ or CD8+ T cells but CD25-. To date, only a single mouse with CD4+CD25+ T cell proliferation during polyclonal expansion of leukemia cells has been observed among the tested mice up to age 21 months. Furthermore, similar to the genesis of lymphoma/leukemia, these mice developed arthropathy. The affected mice showed the swelling of the joints with lesions frequently seen in the hind leg ankles. The lesion showed erosion of the bones and cartilage, inflammatory cell infiltration into the joint space and replacement of pannus-like granulation tissues. These results indicate that Tax can cause two different diseases, T cell leukemia/lymphoma and arthropathy in our model mice.