Genomic location of mouse mammary tumor virus proviral DNA in normal mouse tissue and in mammary tumors.
Genomic location of mouse mammary tumor virus proviral DNA in normal mouse tissue and in mammary tumors.
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小鼠乳腺肿瘤病毒原病毒 DNA 在正常小鼠组织和乳腺肿瘤中的基因组定位。
DOI：
10.1101/sqb.1980.044.01.125
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发表时间：
1980
期刊：
影响因子：
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通讯作者：
Rob Michalides
中科院分区：
文献类型：
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作者：
Nancy E. Hynes;Bernd Groner;H. Diggelmann;R. V. Nie;Rob Michalides
小鼠乳腺肿瘤病毒（MMTV）可作为外源性病毒或内源性病毒传播。内源性病毒通过生殖细胞传给后代，并以原病毒DNA的形式存在于小鼠所有细胞的基因组DNA中。除了GR小鼠株外，这些垂直传播的原病毒序列似乎与早期乳腺肿瘤的形成无关。外源性病毒通过某些小鼠品系（如C3H品系）的乳汁传播。这种乳传播病毒与这些高发病率的乳腺肿瘤毒株的早期肿瘤形成有关（Hilgers和Bentvelzen 1978）。所有测试的近交小鼠株都含有MMTV原病毒DNA序列（Varmus等，1972；Scolnick等，1974；Michalides等，1976；Morris等，1977）。这些序列的起源和功能仍然是推测性的。对不同近交系小鼠株中MMTV原病毒基因组位置的比较研究可能有助于回答这些问题。杂交分析表明，通过乳液传播MMTV的小鼠乳腺肿瘤除了含有内源性拷贝外，还含有MMTV原病毒（Michalides et al. 1976; Morris et al. 1977）。这些被认为是由外源性病毒感染靶细胞，然后逆转录和前病毒整合到基因组DNA中引起的。这些乳腺肿瘤特异性前病毒序列被认为与乳腺肿瘤的形成有关。原病毒DNA表达的控制可能部分基于原病毒整合位点内和周围的初级核苷酸序列。因此，对新获得的原病毒在乳腺肿瘤DNA中的整合位点进行了表征。Southern (1975) DNA过滤转移技术的发展使我们能够研究内源性MMTV前病毒的基因组位置和新获得的前病毒在乳腺肿瘤DNA中的整合位点。GR小鼠品系与其他品系的不同之处在于，一个单一的显性基因Mtv-2既控制乳腺肿瘤的早期出现，也控制乳汁中MMTV抗原的早期表达（Bentvelzen and Daams 1969; Van Nie et al. 1977）。外源性病毒感染不是乳腺肿瘤形成的必要条件。mv -2基因位于18号染色体上，与Tw基因密切相关（R. Van Nie et al., in prep.）。一个同源菌株，
The mouse mammary tumor virus (MMTV) can be transmitted as an exogenous virus or an endogenous virus. The endogenous virus is passed to the offspring via the germ cell and is present as proviral DNA integrated into the genomic DNA in all cells of the mouse. In all but the GR mouse strain, these vertically transmitted proviral sequences do not seem to be involved in early mammary tumor formation. The exogenous virus is transmitted by the milk of certain strains of mice, such as the C3H strain. This milktransmitted virus has been implicated in early tumor formation in these strains with a high incidence of mammary tumors (Hilgers and Bentvelzen 1978). All tested inbred strains of mice contain MMTV proviral DNA sequences (Varmus et al. 1972; Scolnick et al. 1974; Michalides et al. 1976; Morris et al. 1977). The origin and the function of these sequences remain speculative. A comparative study of the genomic location of MMTV proviruses in different inbred mouse strains may be useful in answering these questions. Mammary tumors arising in mice that transmit MMTV via the milk have been shown by hybridization analyses to contain MMTV proviruses in addition to the endogenous copies present (Michalides et al. 1976; Morris et al. 1977). These are assumed to have arisen from exogenous viral infection of target cells followed by reverse transcription and proviral integration into the genomic DNA. These mammary-tumor-specific proviral sequences are thought to be related to mammary tumor formation. The control of the expression of the proviral DNA may be based, in part, on the primary nucleotide sequence within and around the proviral integration site. Therefore, a characterization of the integration sites of the newly acquired proviruses in mammary tumor DNA has been carried out. The development of the Southern (1975) DNA filter-transfer technique has enabled us to study both the genomic location of the endogenous MMTV proviruses and the integration sites of the newly acquired proviruses in mammary tumor DNA. The GR mouse strain is different from other strains, in that a single dominant gene, Mtv-2, controls both the early appearance of mammary tumors and the early expression of MMTV antigens in the milk (Bentvelzen and Daams 1969; Van Nie et al. 1977). Infection by exogenous virus is not necessary for mammary tumor formation. The Mtv-2 gene is located on chromosome 18 and is closely linked with the Tw gene (R. Van Nie et al., in prep.). A congenic strain,