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B型逆转录病毒诱导的胸腺淋巴瘤中的一个常见整合位点。

A common integration locus in type B retrovirus-induced thymic lymphomas.

作者信息

Mueller R E, Baggio L, Kozak C A, Ball J K

机构信息

Department of Biochemistry, University of Western Ontario, London, Canada.

出版信息

Virology. 1992 Dec;191(2):628-37. doi: 10.1016/0042-6822(92)90238-k.

DOI:10.1016/0042-6822(92)90238-k
PMID:1333116
Abstract

Type-B leukemogenic retrovirus (TBLV) is a replication-competent type-B thymotropic retrovirus which lacks a transforming gene and whose genome is > 98% homologous to that of type-B mouse mammary tumor virus (MMTV). In contrast to MMTV, which induces mammary adenocarcinomas, TBLV induces a high incidence of T-cell thymic lymphomas in mice after a very short latent period. To investigate the molecular mechanisms by which TBLV induces T-cell lymphomas, we screened TBLV-induced tumor DNA for the frequent disruption of a particular cellular locus by TBLV proviral copies. In approximately 20% of the 55 primary tumors screened, the presence of proviruses in a common integration site was detected. This locus spans at least 53 kb of genomic DNA and maps to the mouse X chromosome. The presence of a functional gene at this locus is suggested by the conservation of nucleotide sequences from this locus among diverse animal species and by the expression of these sequences as mRNA in normal mouse tissues and tumors. The majority (17/18) of TBLV-induced primary tumors examined have elevated levels of this expressed mRNA.

摘要

B型白血病逆转录病毒(TBLV)是一种具有复制能力的嗜胸腺B型逆转录病毒,它缺乏转化基因,其基因组与B型小鼠乳腺肿瘤病毒(MMTV)的基因组同源性>98%。与诱导乳腺腺癌的MMTV不同,TBLV在很短的潜伏期后就能在小鼠中诱导出高发病率的T细胞胸腺淋巴瘤。为了研究TBLV诱导T细胞淋巴瘤的分子机制,我们筛选了TBLV诱导的肿瘤DNA,以寻找TBLV前病毒拷贝对特定细胞位点的频繁破坏。在筛选的55个原发性肿瘤中,约20%检测到前病毒存在于一个共同的整合位点。该位点跨越至少53 kb的基因组DNA,定位于小鼠X染色体。不同动物物种中该位点核苷酸序列的保守性以及这些序列在正常小鼠组织和肿瘤中作为mRNA的表达,提示该位点存在一个功能基因。所检测的大多数(17/18)TBLV诱导的原发性肿瘤中,这种表达的mRNA水平升高。

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