A Moloney murine leukemia virus-based retrovirus with 4070A long terminal repeat sequences induces a high incidence of myeloid as well as lymphoid neoplasms
A Moloney murine leukemia virus-based retrovirus with 4070A long terminal repeat sequences induces a high incidence of myeloid as well as lymphoid neoplasms
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DOI：
10.1128/jvi.77.8.4965-4971.2003
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发表时间：
2003-04-01
影响因子：
5.4
通讯作者：
Anver, MR
中科院分区：
文献类型：
--
作者：
Wolff, L;Koller, R;Anver, MR
逆转录病毒可以被用来加速通过先前的遗传操作而容易患上肿瘤的造血癌，例如在转基因或基因敲除小鼠中。该病毒提供了第二次肿瘤“袭击”，提供了最初的袭击正在转变的证据。在本研究中，一种独特的逆转录病毒被开发出来，它可以诱导高发病率的髓系疾病，并具有广泛的宿主范围。这种药物是一种基于莫洛尼小鼠白血病病毒(Mo-MuLV)的病毒，它的大部分长末端重复序列(LTR)的U3区域被逆转录病毒4070A的U3区域取代。与Mo-MuLV一样，这种名为MOL4070LTR的病毒是嗜NB的，不受Fv1亚种的限制。MOL4070LTR会导致大约50%的小鼠患上髓系白血病，这一发现与Mo-MuLV形成鲜明对比，Mo-MuLV几乎只会导致淋巴疾病。这些数据表明，4070A病毒的LTR将疾病的组织嗜性扩大到髓系。有趣的是，MCF重组包膜在BALB/c小鼠的淋巴系肿瘤中表达，而在髓系肿瘤中不表达。这种逆转录病毒有可能加速基因工程小鼠的髓系疾病。
Retroviruses can be used to accelerate hematopoietic cancers predisposed to neoplastic disease by prior genetic manipulations such as in transgenic or knockout mice. The virus imparts a second neoplastic "hit," providing evidence that the initial hit is transforming. In the present study, a unique retrovirus was developed that can induce a high incidence of myeloid disease and has a broad host range. This agent is a Moloney murine leukemia virus (Mo-MuLV)-based virus that has most of the U3 region of the long terminal repeat (LTR) replaced with that of retrovirus 4070A. Like Mo-MuLV, this virus, called MOL4070LTR, is NB-tropic and not restricted by Fv1 allelles. MOL4070LTR causes myeloid leukemias in ca. 50% of mice, a finding in contrast to Mo-MuLV, which induces almost exclusively lymphoid disease. The data suggest that the LTR of the 4070A virus expands the tissue tropism of the disease to the myeloid lineage. Interesting, MCF recombinant envelope was expressed in the lymphoid but not the myeloid neoplasms of BALB/c mice. This retrovirus has the potential for accelerating myeloid disease in genetically engineered mice.