EARLY REGIONS OF JC VIRUS AND BK VIRUS INDUCE DISTINCT AND TISSUE-SPECIFIC TUMORS IN TRANSGENIC MICE
EARLY REGIONS OF JC VIRUS AND BK VIRUS INDUCE DISTINCT AND TISSUE-SPECIFIC TUMORS IN TRANSGENIC MICE
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DOI：
10.1073/pnas.83.21.8288
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发表时间：
1986-11-01
影响因子：
11.1
通讯作者：
SCANGOS, GA
中科院分区：
文献类型：
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作者：
SMALL, JA;KHOURY, G;SCANGOS, GA
JC病毒和BK病毒是普遍存在的人类病毒，与猿猴病毒40具有序列和结构同源性。为了表征这些病毒的组织特异性表达并建立用于研究人类病毒诱导的疾病的模型系统，产生了含有每种病毒的早期区域的转基因小鼠。这些病毒序列以独特的组织特异性方式诱导肿瘤，这与它们在人类中的组织嗜性相似。产生了10只含JC病毒的创始小鼠，其中5只存活至成熟。其中4例发生肾上腺神经母细胞瘤，转移到其他几个组织。JC病毒肿瘤抗原RNA在这些小鼠的肿瘤组织中检测到高水平，在其他正常组织中检测到低水平。三只含BK病毒的小鼠中有一只形状异常，在2周龄时死亡。另外两只含有BK病毒的小鼠发生原发性肝细胞癌和肾肿瘤，并在8 - 10个月大时死亡。BK病毒肿瘤抗原RNA在两种小鼠的肿瘤组织中表达。由于每种病毒都保留了它在人类中表现出的一般组织嗜性，这些数据表明，携带人类病毒的转基因小鼠将可用作病毒诱导疾病的动物模型。
JC virus and BK virus are ubiquitous human viruses that share sequence and structural homology with simian virus 40. To characterize tissue-specific expression of these viruses and to establish model systems for the study of human viral-induced disease, transgenic mice containing early regions of each of the viruses were produced. The viral sequences induced tumors in a distinct and tissue-specific manner that was similar to their tissue tropism in humans. Ten JC virus-containing founder mice were produced, of which 5 survived to maturity. Four of them developed adrenal neuroblastomas, which metastasized to several other tissues. JC virus tumor-antigen RNA was detected at high levels in the tumor tissues and at low levels in other normal tissues of these mice. One of the three BK virus-containing mice was abnormally shaped and died at 2 weeks of age. The other two BK virus-containing mice developed primary hepatocellular carcinomas and renal tumors and died at 8-10 months of age. BK virus tumor-antigen RNA was expressed in tumor tissues of both mice. Since each of the viruses retained the general tissue tropism that it exhibits in humans, these data suggest that transgenic mice harboring human viruses will be useful as animal models for viral-induced diseases.