Popp R A, Bailiff E G, Skow L C, Johnson F M, Lewis S E
Genetics. 1983 Sep;105(1):157-67. doi: 10.1093/genetics/105.1.157.
A DBA/2 mouse treated with ethylnitrosourea sired an offspring whose hemoglobin showed an extra band following starch gel electrophoresis. The variant hemoglobin migrated to a more cathodal position in starch gel. Isoelectric focusing indicated that chain 5 of the mutant hemoglobin migrated to a more cathodal position than the normal chain 5 from DBA/2 mice and that the other alpha-globin, chain 1, was not affected. On focusing gels the phenotype of the mutant allele, Hbay9, was expressed without dominance to normal chain 5, and Hbay9/Hbay9 homozygotes were fully viable in the laboratory. The molecular basis for the germinal mutation was investigated by analyzing the amino acid sequence of chain 5y9, the mutant form of alpha-chain 5. A single amino acid substitution (His leads to Leu) at position 89 was found in chain 5y9. We propose that ethylnitrosourea induced an A leads to T transversion in the histidine codon at position 89 (CAC leads to CTC). This mutation has apparently not been observed previously in humans, mice or other mammals, and its novel occurrence may be indicative of other unusual mutational events that do not ordinarily occur in the absence of specific mutagen exposure.
一只用乙基亚硝基脲处理过的DBA/2小鼠生下了一只后代，其血红蛋白在淀粉凝胶电泳后显示出一条额外的条带。这种变异血红蛋白在淀粉凝胶中向更阴极的位置迁移。等电聚焦表明，突变血红蛋白的5链比DBA/2小鼠的正常5链向更阴极的位置迁移，而另一条α珠蛋白链1不受影响。在聚焦凝胶上，突变等位基因Hbay9的表型表达时对正常5链没有显性，并且Hbay9/Hbay9纯合子在实验室中完全存活。通过分析α链5的突变形式5y9链的氨基酸序列，研究了生殖系突变的分子基础。在5y9链中发现第89位有一个单一的氨基酸取代（组氨酸变为亮氨酸）。我们推测乙基亚硝基脲在第89位的组氨酸密码子（CAC变为CTC）中诱导了A到T的颠换。这种突变以前在人类、小鼠或其他哺乳动物中显然没有观察到，它的新出现可能表明在没有特定诱变剂暴露的情况下通常不会发生的其他异常突变事件。
