Analysis of a mouse. cap 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 posititon 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 ..cap alpha..-globin, chain 1, was not affected. On focusing gels the phenotype of the mutant allele, Hba/sup y9/, was expressed without dominance to normal chain 5, and Hba/sup y9/ / Hba/sup y9/ homozygotes were fully viable in the laboratory. The molecular basis for the germinal mutation was investigated by analyzing the amino acid sequence of chain 5/sup y9/, the mutant form of ..cap alpha..-chain 5. A single amino acid substitution (His ..-->.. Leu) at position 89 was found in chain 5/sup y9/. The authors propose that ethylnitrosourea induced an A ..-->.. T transversion in the histidine codon at position 89 (CAC ..-->.. 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.
- Research Organization:
- Oak Ridge National Lab., TN
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 6214482
- Journal Information:
- Genetics; (United States), Vol. 105
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HEMOGLOBIN
MUTATIONS
NITROSOUREAS
MUTAGENESIS
AMINO ACID SEQUENCE
CODONS
ELECTROPHORESIS
GENES
MICE
MOLECULAR BIOLOGY
PHENOTYPE
ANIMALS
CARBOXYLIC ACIDS
GLOBIN
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
MAMMALS
MOLECULAR STRUCTURE
NITROSO COMPOUNDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIGMENTS
PORPHYRINS
PROTEINS
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)