CHROMOSOMAL POSITION AND ACTIVATION OF RETROVIRAL GENOMES INSERTED INTO THE GERM LINE OF MICE
CHROMOSOMAL POSITION AND ACTIVATION OF RETROVIRAL GENOMES INSERTED INTO THE GERM LINE OF MICE
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DOI：
10.1016/0092-8674(81)90343-3
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发表时间：
1981-01-01
期刊：
影响因子：
64.5
通讯作者：
GROTKOPP, D
中科院分区：
文献类型：
--
作者：
JAENISCH, R;JAHNER, D;GROTKOPP, D
将外源性莫洛尼白血病病毒（M-MuLV）通过在胚胎发育的不同阶段暴露于病毒而插入到小鼠的生殖系中。来自暴露胚胎的小鼠在整合病毒方面是嵌合体。九个新的亚株，命名为MOV-5至MOV-13，衍生，其中每一个携带一个单一的M-MuLV基因组在其生殖系的不同染色体位置。先前衍生了四个亚株，Mov-1至Mov-4。限制性内切酶分析表明，除MOV-4和MOV-6小鼠外，在整合的前病毒基因组中未发生重大重排或缺失。感染性病毒在大多数亚株（Mov-4至Mov-8和Mov-10至Mov-12）中不被激活，而其他小鼠则出现病毒血症。对MOV-1和MOV-13小鼠的详细比较表明，病毒活化的时间不同。Mov-13小鼠在胚胎发生过程中激活感染性病毒，导致成年小鼠所有组织中病毒表达的独特模式，但Mov-1小鼠中的病毒基因组仅在出生后的前2周内激活，导致病毒主要在淋巴器官中表达。与先前的观察结果一起，在13个亚株中可以区分出至少4种不同的病毒表达表型（胚胎发生期间的早期病毒活化、出生后的病毒活化、生命后期的病毒活化和完全不表达感染性病毒）。病毒基因组整合的染色体区域明显影响其在发育和分化过程中的表达。
The exogenous Moloney leukemia virus (M-MuLV) was inserted into the germ line of mice by exposing embryos to virus at different stages of embryogenesis. Mice derived from exposed embryos were mosaics with respect to integrated virus. Nine new substrains, designated Mov-5 to Mov-13, were derived, each of which carries a single M-MuLV genome at a different chromosomal position in its germ line. Four substrains, Mov-1 to Mov-4, were derived previously. Restriction enzyme analyses demonstrated that, with the exception of Mov-4 and Mov-6 mice, no major rearrangements or deletions have occurred in the integrated proviral genomes. Infectious virus is not activated in the majority of substrains (Mov-4 to Mov-8 and Mov-10 to Mov-12), whereas the other mice develop viremia. A detailed comparison between Mov-1 and Mov-13 mice demonstrated that the time of virus activation is different. Mov-13 mice activate infectious virus during embryogenesis, leading to a distinct pattern of virus expression in all tissues of the adult, but the viral genome in Mov-1 mice is activated only during the first 2 wk after birth, leading to virus expression predominantly in lymphatic organs. Together with previous observations, at least 4 different phenotypes of virus expression (early virus activation during embryogenesis, virus activation after birth, virus activation late in life and no expression of infectious virus at all) can be distinguished among the 13 substrains. The chromosomal region at which a viral genome is integrated apparently influences its expression during development and differentiation.