Morphological, histochemical, immunohistochemical, and ultrastructural characterization of tumors and dysplastic and non-neoplastic lesions arising in BK virus/tat transgenic mice
Morphological, histochemical, immunohistochemical, and ultrastructural characterization of tumors and dysplastic and non-neoplastic lesions arising in BK virus/tat transgenic mice
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DOI：
10.1016/s0002-9440(10)65375-8
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发表时间：
1999-04-01
影响因子：
6
通讯作者：
Corallini, A
中科院分区：
文献类型：
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作者：
Altavilla, G;Trabanelli, C;Corallini, A
为了研究人类免疫缺陷病毒1型（HIV-1）达特蛋白（病毒和细胞基因的反式激活因子）在艾滋病发病机制中的作用，我们用含有BK病毒（BKV）早期区和HIV-1 tat基因的重组DNA构建了转基因小鼠，并由其自身的启动子-增强子指导。DNA杂交显示，转基因是稳定地保持在所有器官的转基因小鼠作为一个串联插入的拷贝数范围从5至20个每个细胞。此外，达特和BKV RNA在所有组织中表达。转基因小鼠产生三种类型的病变：1）肿瘤，2）增生和发育不良病变，和3）非肿瘤性病变。不同组织型的肿瘤，如淋巴瘤、皮肤腺腺癌、平滑肌瘤、皮肤鳞状细胞癌、肝癌、肝癌和海绵状肝血管瘤，在29%的转基因动物中发生。大多数肿瘤是恶性的，侵袭性的，并产生转移，相反，只有两种组织型的肿瘤（淋巴瘤和皮肤腺体腺癌）出现在对照组小鼠。与对照小鼠相比，在转基因小鼠中增生和发育异常病变更常见，并且涉及皮肤或其附件、肝脏和直肠，表明转基因活性的多个靶点，肾盂肾炎，经常并发肾积水、炎性眼部病变和淀粉样蛋白沉积是在转基因小鼠中检测到的最常见的非肿瘤性病变。在该动物模型中观察到的许多病理学发现与AIDS患者中出现的类似病变相当，表明达特在AIDS过程中在此类病变的发病机制中具有相关作用。
To study the role in AIDS pathogenesis of the human immunodeficiency virus type 1 (HIV-1) Tat protein, a transactivator of viral and cellular genes, we generated transgenic mice with a recombinant DNA containing BK virus (BKV) early region and the HIV-1 tat gene, directed by its own promoter-enhancer. DNA hybridization revealed that the transgene is stably maintained in all organs of transgenic mice as a tandem insertion in a number of copies ranging from 5 to 20 per cell. In addition, tat and BKV RNA were expressed in all tissues. Transgenic mice developed three types of lesions: 1) tumors, 2) hyperplastic and dysplastic lesions, and 3) non-neoplastic lesions. Tumors of different histotypes, such as lymphomas, adenocarcinomas of skin glands, leiomyosarcomas, skin squamous cell carcinomas, hepatomas, hepato carcinomas, and cavernous Liver hemangiomas, developed in 29% of transgenic animals. The majority of tumors were malignant, invasive, and producing metastases, Conversely, tumors of only two histotypes (lymphomas and adenocarcinomas of skin glands) appeared in control mice. Hyperplastic and dysplastic lesions were more frequent in transgenic than in control mice and involved the skin or its adnexes, the liver and the rectum, indicating multiple targets for the activity of the transgene, Pyelonephritis, frequently complicated with hydronephrosis, inflammatory eye lesions, and amyloid depositions represented the most frequent non-neoplastic lesions detected in transgenic mice. Many of the pathological findings observed in this animal model are comparable to similar lesions appearing in AIDS patients, suggesting a relevant role for Tat in the pathogenesis of such lesions during the course of AIDS.