Two dominant mutations in the mouse fused gene are the result of transposon insertions.
Two dominant mutations in the mouse fused gene are the result of transposon insertions.
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发表时间：
1997-10
期刊：
影响因子：
3.3
通讯作者：
Thomas J. Vasicek;Li Zeng;X. Guan;Tong Zhang;Frank Costantini;Shirley M. Tilghman
中科院分区：
文献类型：
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作者：
Thomas J. Vasicek;Li Zeng;X. Guan;Tong Zhang;Frank Costantini;Shirley M. Tilghman
小鼠的融合基因编码了一种蛋白质，该蛋白质与胚轴形成的调节有关。这种蛋白质被命名为Axin，以区别于无关的果蝇黑腹果蝇基因融合的产物，它含有与RGS(G蛋白信号调节因子)家族以及Disheveled相似的区域，Disheveled是黑腹果蝇Wingless下游的一种蛋白质。融合基因的功能丧失突变会导致怀孕8至10天的死亡。三个显性突变导致杂合子的尾巴扭结。两个显性突变，融合和Knobble，是由脑池内A粒子反转录转座子插入基因造成的。在第六内含子内的融合插入，创造了一个基因，产生野生型转录本和突变型转录本，这些转录本既始于真正的启动子，也始于插入的3‘-最长末端重复序列。令人费解的是，反转录转座子插入到外显子7中，排除了野生型蛋白的产生。因此，融合的纯合子是可行的，而诺布利是隐性胚胎致死的。在这两个突变体中，主要的扭尾表型可能是由于合成了类似的Axin蛋白氨基末端片段而导致的，这些片段包含RGS结构域，但缺乏凌乱的结构域。
The mouse Fused locus encodes a protein that has been implicated in the regulation of embryonic axis formation. The protein, which has been named Axin to distinguish it from the product of the unrelated Drosophila melanogaster gene fused, contains regions of similarity to the RGS (regulators of G-protein signaling) family of proteins as well as to dishevelled, a protein that acts downstream of Wingless in D. melanogaster. Loss-of-function mutations at Fused lead to lethality between days 8 and 10 of gestation. Three dominant mutations result in a kinked tail in heterozygotes. Two of the dominant mutations, Fused and Knobbly, result from insertion of intracisternal A particle retrotransposons into the gene. The insertion in Fused, within the sixth intron, creates a gene that produces wild-type transcripts as well as mutant transcripts that initiate at both the authentic promoter and the 3'-most long terminal repeat of the insertion. Knobbly, an insertion of the retrotransposon into exon 7, precludes the production of wild-type protein. Thus the Fused homozygote is viable whereas Knobbly is a recessive embryonic lethal. In both mutants the dominant kink-tailed phenotype is likely to result from the synthesis of similar amino-terminal fragments of Axin protein that would contain the RGS domain, but lack the dishevelled domain.