Gustavson E, Goldsborough A S, Ali Z, Kornberg T B
Department of Biochemistry and Biophysics, University of California, San Francisco 94143, USA.
Genetics. 1996 Mar;142(3):893-906. doi: 10.1093/genetics/142.3.893.
We isolated and characterized numerous engrailed and invected alleles. Among the deficiencies we isolated, a mutant lacking invected sequences was viable and phenotypically normal, a mutant lacking engrailed was an embryo lethal and had slight segmentation defects, and a mutant lacking both engrailed and invected was most severely affected. In seven engrailed alleles, mutations caused translation to terminate prematurely in the central or C-terminal portion of the coding sequence, resulting in embryonic lethality and segmentation defects. Both engrailed and invected expression declined prematurely in these mutant embryos. In wild-type embryos, engrailed and invected are juxtaposed and are expressed in essentially identical patterns. A breakpoint mutant that separates the engrailed and invected transcription units parceled different aspects of the expression pattern to engrailed or invected. We also found that both genes cause similar defects when expressed ectopically and that the protein products of both genes act to repress transcription in cultured cells. We propose that the varied phenotypes of the engrailed alleles can be explained by the differential effects these mutants have on the combination of engrailed and invected activities, that engrailed and invected share a regulatory region, and that they encode redundant functions.
我们分离并鉴定了许多engrailed和invected等位基因。在我们分离出的缺失突变体中，一个缺少invected序列的突变体是可存活的且表型正常，一个缺少engrailed的突变体胚胎致死且有轻微的体节缺陷，而一个同时缺少engrailed和invected的突变体受影响最为严重。在七个engrailed等位基因中，突变导致编码序列的中部或C端部分翻译提前终止，从而导致胚胎致死和体节缺陷。在这些突变胚胎中，engrailed和invected的表达均过早下降。在野生型胚胎中，engrailed和invected相邻并以基本相同的模式表达。一个将engrailed和invected转录单位分开的断点突变体将表达模式的不同方面分配给了engrailed或invected。我们还发现，当异位表达时，这两个基因会导致相似的缺陷，并且这两个基因的蛋白质产物在培养细胞中都具有抑制转录的作用。我们提出，engrailed等位基因的不同表型可以通过这些突变体对engrailed和invected活性组合的不同影响来解释，engrailed和invected共享一个调控区域，并且它们编码冗余功能。
