权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of HTLV-I Tax transgenic mice as an animal model for adult T-cell leukemia by using T cell specific gene promoter.

通过使用 T 细胞特异性基因启动子开发 HTLV-I Tax 转基因小鼠作为成人 T 细胞白血病的动物模型。

基本信息

批准号：
12680816
负责人：
OHSUGI Takeo
金额：
$ 1.98万
依托单位：
Kumamoto University (2001-2002)Juntendo University (2000)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680816/
关键词：
HTLV-I Tax mice transgenic mice Lck

项目摘要

Human T-cell leukemia virus type I (HTLV-I) is a causative agent that induces adult T-cell leukemia/lymphoma (ATL). To investigate the therapeutic agent for ATL, it is necessary to establish an animal model. The HTLV-I regulatory protein Tax has been postulated to lead to the proliferation and transformation of T-cells in ATL. In this study, we attempted to develop transgenic (Tg) mice expressing HTLV-I Tax preferentially in T-cells under the control of a distal or proximal lck promoter that direct high expression in mature or immature T-cells, respectively. Tumors developed on the liver and lung of proximal-Tax #15, and on the liver, spleen and lung of distal-Tax #6. These tumors were not derived from T-cells. Histological examination of kidneys in proximal-Tax #15 and #16, distal-Tax #6 and #7 showed glomerular nephritis, whereas the nontransgenic mice had no lesion. No transgenic progeny were obtained from these founder mice. Therefore, offspring with Tax gene was obtained using in vivo fertilization technique in proximal-Tax Tg mice, and the change of genetic background of distal-Tax Tg mice from C57BL/6 to BDF1 produced offspring with Tax gene. Pathological and molecular biological analyses of these mice are in progress at our laboratory.

人T细胞白血病病毒I型(HTLV-I)是引起成人T细胞白血病/淋巴瘤(ATL)的病原体。为了研究ATL的治疗药物，建立动物模型是必要的。HTLV-I调节蛋白Tax被认为可以导致ATL中T细胞的增殖和转化。在这项研究中，我们试图在远端或近端的Lck启动子的控制下，分别在成熟和未成熟的T细胞中高表达HTLV-I Tax的转基因(TG)小鼠。肿瘤发生在近端税号15的肝脏和肺，以及远端税号6的肝、脾和肺。这些肿瘤不是来自T细胞。近端税#15和#16，远端税#6和#7的肾脏组织学检查显示肾小球肾炎，而非转基因小鼠没有病变。这些创始小鼠均未获得转基因后代。因此，利用体内受精技术在近端Tax-Tg小鼠中获得了携带Tax基因的后代，而远端Tax-Tg小鼠的遗传背景从C57BL/6向BDF1的改变产生了携带Tax基因的后代。我们实验室正在对这些小鼠进行病理和分子生物学分析。