ANALYSIS OF HTLV-I PATHOGENICITY USING ANIMAL MODELS

利用动物模型分析 HTLV-I 致病性

基本信息

批准号：
06454188
负责人：
YOSHIKI Takashi
金额：
$ 4.22万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454188/
关键词：
HTLV-I Disease Model HAM TSP Demyelination Apoptosis Transgenic Rat Mammary Carcinoma Autoimmune Diseases HTLV-I

项目摘要

To investigate the pathogenesis of HTLV-I associated diseases, three rat models, HAM rat for HAM/TSP,mammary carcinoma developed pX rat for HTLV-I tumorigenicity, and autoimmune diseases developed env-pX rat for HTLV-I associated immunological disorders, were established by HTLV-I infection or transgenic technique.1) HAM rat : In the spinal cords of WKAH rats carrying HTL-I infection, the apoptotic death of oligodendrocytes starting at 9 months after the infection was the first histopathological event before the demyelination. pX was selectively expressed in the diseased leasions, but not in others, even though provirus DNAs were consistently identified. TNF-alpha were frequently expressed in the diseased lesions. Moreover, both pX and TNF-alpha were expressed in the target leasions from 7 months after the infection. The collective evidence suggests that the apoptotic death of myelin forming cells in the target leasions by the selective activation of pX,and/or the production of TNF-alp … More ha is a major pathogenetic pathway of HAM rat disease.2) pX rat : In transgenic rats carrying the pX gene under control of the mouse H-2 promoter, undifferentiated mammary carcinomas with granulocytic infiltration developed starting at 5 months of age. mRNAs of both pX and host genes, Gro and MIP-2, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and anti-oncogene were not demonstrated, hitherto unidentified novel oncogenic pathways may be activated in these pX rats.3) env-pX rat : Transgenic rats carrying the env-pX gene, under control of own LTR,were established. Starting at 5 weeks of age, arthritis resembling RA,necrotizing arteritis resembling PN,polymyositis, myocarditis and Sjogren's syndrome-like sialo-and dacryoadenitis developed in env-pX rats. Thymic atrophy with severe depletion of CD4CD8 positive thymocytes was also observed. Autosntibodies, including rheumatoid factors and anti-dsDNA and anti-cardiolipin antibodies, were detected in the serum. The evidence indicztes that HTLV-I env-pX gene may cause these immunological disorders with autoimmune phenomenon. Less

为了研究 HTLV-I 相关疾病的发病机制，建立了三种大鼠模型：针对 HAM/TSP 的 HAM 大鼠模型、针对 HTLV-I 致瘤性的乳腺癌开发的 pX 大鼠模型以及针对 HTLV-I 相关免疫性疾病开发的自身免疫性疾病 env-pX 大鼠模型。 1) HAM大鼠：在携带HTL-I感染的WKAH大鼠的脊髓中，细胞凋亡感染后 9 个月开始的少突胶质细胞是 pX 在病变病变中选择性表达之前的第一个组织病理学事件，但在其他病变中则不然，尽管原病毒 DNA 经常在病变病变中表达。此外，感染后 7 个月，pX 和 TNF-α 在靶病灶中表达，集体证据表明髓鞘形成细胞凋亡。通过选择性激活 pX 和/或 TNF-alp 的产生来实现靶病变。 ha 是 HAM 大鼠疾病的主要致病途径。2) pX 大鼠：在小鼠 H 控制下携带 pX 基因的转基因大鼠-2 启动子，即具有粒细胞浸润的未分化乳腺癌，从 5 个月大开始，pX 和宿主基因 Gro 和 MIP-2 的 mRNA 在肿瘤组织中高表达。一些致癌基因和抗癌基因的表达和点突变尚未得到证实，迄今为止未识别的新型致癌途径可能在这些 pX 大鼠中被激活。 3) env-pX 大鼠：携带 env-pX 基因的转基因大鼠，在自身 LTR 的控制下，从 5 周龄开始，出现类似 RA 的关节炎、类似 PN 的坏死性动脉炎、多发性肌炎、心肌炎和env-pX 大鼠出现类似干燥综合征的唾液腺炎和泪腺炎，并在血清中检测到自身抗体，包括类风湿因子、抗 dsDNA 和抗心磷脂抗体。表明HTLV-I env-pX基因可能导致这些具有自身免疫现象的免疫紊乱。较少的