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首页> 外文期刊>Experimental Animals >Analysis of T cell leukemia/lymphoma in a human T-cell leukemia virus type I tax gene transgenic mouse model
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Analysis of T cell leukemia/lymphoma in a human T-cell leukemia virus type I tax gene transgenic mouse model

机译：人类T细胞白血病病毒I型tax基因转基因小鼠模型中T细胞白血病/淋巴瘤的分析

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Adult T-cell leukemia (ATL) is a peripheral CD4 positive T cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I). The Tax protein encoded by the pX region of HTLV-I is likely responsible for the development of ATL. The best way to investigate the role of the Tax in pathogenesis in vivo is to produce transgenic (Tg) mouse models expressing tax gene. We generated transgenic mice that expressed the tax gene driven by a mouse lymphocyte-specific protein-tyrosine kinase (Lck) distal promoter. Real-time RT-PCR analysis showed expression of the tax transgene in the thymus and spleen. Over a two-year period, we studied 105 transgenic offspring from one of the two leukemic founders. Of these mice, 25.7% (27/105) developed T-cell leukemia/lymphoma with marked splenomegaly, hepatomegaly and lymphadenopathy. The total white blood cell count was significantly elevated, and large and abnormal leukemic cells comprised >80% of the peripheral blood mononuclear cells. The clonal population of leukemic cells was comprised of either CD4~+ or CD8~+ T cells; all cells examined were CD25~+. Because hypercalcemia is frequently observed in ATL patients, we also measured serum calcium in leukemic mice and found it to be significantly higher than in control mice. The leukemic cells in Tg mice showed marked NF-κB activity. These results suggested that Tax expression alone in Tg mice is sufficient to develop T cell leukemia/lymphoma.
机译：成人T细胞白血病（ATL）是由人I型T细胞白血病病毒（HTLV-1）引起的外周CD4阳性T细胞肿瘤。由HTLV-1的pX区编码的Tax蛋白可能负责ATL的发展。研究Tax在体内发病机理中的作用的最佳方法是产生表达tax基因的转基因（Tg）小鼠模型。我们生成了表达由小鼠淋巴细胞特异性蛋白酪氨酸激酶（Lck）远端启动子驱动的tax基因的转基因小鼠。实时RT-PCR分析显示，在胸腺和脾脏中表达了tax转基因。在两年的时间里，我们研究了来自两位白血病创始人之一的105个转基因后代。在这些小鼠中，有25.7％（27/105）患上T细胞白血病/淋巴瘤，并伴有明显的脾肿大，肝肿大和淋巴结肿大。总白细胞计数显着升高，并且大而异常的白血病细胞占外周血单核细胞的> 80％。白血病细胞的克隆群由CD4〜+或CD8〜+ T细胞组成。所有检查的细胞均为CD25〜+。因为在ATL患者中经常观察到高钙血症，所以我们还测量了白血病小鼠的血清钙，发现它明显高于对照组小鼠。 Tg小鼠的白血病细胞显示出明显的NF-κB活性。这些结果表明，仅在Tg小鼠中进行Tax表达足以发展T细胞白血病/淋巴瘤。

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