TRANSGENES AS PROBES FOR ACTIVE CHROMOSOMAL DOMAINS IN MOUSE DEVELOPMENT
TRANSGENES AS PROBES FOR ACTIVE CHROMOSOMAL DOMAINS IN MOUSE DEVELOPMENT
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DOI：
10.1038/333852a0
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发表时间：
1988-06-30
期刊：
影响因子：
64.8
通讯作者：
SURANI, MA
中科院分区：
文献类型：
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作者：
ALLEN, ND;CRAN, DG;SURANI, MA
胚胎发育需要一个明确的时间和空间的基因表达计划，这可能会受到活跃的染色体结构域的影响。这些染色体结构域可以利用随机整合到整个基因组的转基因来检测，因为它们的表达会受到染色体位置1-3的影响。位置效应可能对不包含强启动子、增强子或其他调控序列的转基因最强。在这里，我们系统地研究了使用带有弱单纯疱疹病毒胸苷激酶启动子的转基因，连接到容易看到的lacZ指示器基因(HSV-TK-lacZ)的位置效应。每个可检测到表达的转基因胎儿都显示了唯一的elacZ染色模式。因此，这个结构的表达显然完全由它的染色体位置决定，没有任何结构特异性。此外，转基因被忠实地传递给后代，允许系统地绘制出发育期间和成年生活中表达变化的图谱。这些结果表明，转基因确实可以成为探测基因组中活跃的染色体区域的强大工具，具有识别参与器官发生和模式形成的内源基因的潜力。
Embryonic development entails a well defined temporal and spatial programme of gene expression, which may be influenced by active chromosomal domains. These chromosomal domains can be detected using transgenes which integrate randomly throughout the genome, as their expression can be affected by chromosomal position1–3. Position effects are probably exerted most strongly on transgenes that do not contain strong promoters, enhancers or other modulating sequences. Here we have systematically explored position effects using a transgene with the weak herpes-simplex-virus thymidine-kinase promoter, linked to the readily visualizedlacZindicator gene (HSV-TK-lacZ). Each transgenic fetus with detectable expression displayed a uniquelacZstaining pattern. Thus expression of this construct is apparently dictated entirely by its chromosomal position, without any construct specificity. Furthermore the transgene is faithfully transmitted to subsequent generations, allowing for systematic mapping of changes in expression during development and in adult life. These results demonstrate that transgenes can indeed be powerful tools to probe the genome for active chromosomal regions, with the potential for identifying endogenous genes involved in organogenesis and pattern formation.