Analysis of a mouse alpha-globin gene mutation induced by ethylnitrosourea.
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.
D000595:Amino Acid Sequence; D000818:Animals; D002852:Chromatography, Ion Exchange; D004592:Electrophoresis, Starch Gel; D005038:Ethylnitrosourea / Q000494:pharmacology*; D005914:Globins / Q000235:genetics* / Q000302:isolation & purification; D007525:Isoelectric Focusing; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA / Q000097:blood / Q000235:genetics*; D009154:Mutation; D009607:Nitrosourea Compounds / Q000494:pharmacology*
D009607:Nitrosourea Compounds; D005914:Globins; D005038:Ethylnitrosourea