PATTERNS OF EXPRESSION OF POSITION-DEPENDENT INTEGRATED TRANSGENES IN MOUSE EMBRYO
PATTERNS OF EXPRESSION OF POSITION-DEPENDENT INTEGRATED TRANSGENES IN MOUSE EMBRYO
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DOI：
10.1073/pnas.87.16.6331
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发表时间：
1990-08-01
影响因子：
11.1
通讯作者：
NICOLAS, JF
中科院分区：
文献类型：
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作者：
BONNEROT, C;GRIMBER, G;NICOLAS, JF
将外源DNA引入小鼠基因组并在单细胞水平上可视化基因表达的能力是定义遗传程序单个元素的方法的基础。我们描述了使用大肠杆菌lacZ报告基因融合的基因的启动子的次黄嘌呤磷酸核糖转移酶，在所有组织中表达。大多数转基因小鼠（7个中的6个）用该构建体获得，表达来自次黄嘌呤磷酸核糖基转移酶启动子的lacZ基因。然而，出乎意料的是，表达是时间和空间调节的。每个转基因株系的特征在于lacZ表达的特异性、高度可重复的模式。这些结果表明，为了表达，整合的构建体必须由基因组的元件补充。这些因素施加显性发育控制次黄嘌呤磷酸核糖转移酶启动子。一些转基因小鼠的表达模式符合类型学标记，而另一些则符合类型学和地形学的微妙组合。这些观察定义了细胞类型和某些结构的离散异质性，特别是在神经系统和中胚层中。该系统通过提供细胞类型、细胞状态和来自发育隔室的细胞的细胞、分子和遗传标记为发育研究打开了机会。最后，这种方法表明，基因转导或转座到基因组中的不同位置，获得不同的基因组中的位置获得不同的时空特异性，结果具有进化的影响。
The abilities to introduce foreign DNA into the genome of mice and to visualize gene expression at the single-cell level underlie a method for defining individual elements of a genetic program. We describe the use of an Escherichia coli lacZ reporter gene fused to the promoter of the gene for hypoxanthine phosphoribosyl transferase that is expressed in all tissues. Most transgenic mice (six of seven) obtained with this construct express the lacZ gene from the hypoxanthine phosphoribosyltransferse promoter. Unexpectedly, however, the expression is temporally and spatially regulated. Each transgenic line is characterized by a specific, highly reproducible pattern of lacZ expression. These results show that, for expression, the integrated construct must be complemented by elements of the genome. These elements exert dominant developmental control on the hypoxanthine phosphoribosyltransferase promoter. The expression patterns in some transgenic mice conform to a typological maker and in others to a subtle combination of typology and topography. These observations define discrete heterogeneities of cell types and of certain structures, particularly in the nervous system and in the mesoderm. This system opens opportunities for developmental studies by providing cellular, molecular, and genetic makers of cell types, cell states, and cells from developmental compartments. Finally this method illustrates that genes transduced or transposed to a different position in the genome acquire different position in the genome acquire different spatiotemporal specificities, a result that has implications for evolution.