Detection of heritable mutations as quantitative changes in protein expression

A computerized search for the appearance of heritable mutations (as indicated by changes in protein expression) was conducted on three sets of mice, whose sires had been either untreated, exposed to 3 gray units of gamma radiation, or treated with 150 mg/kg ethylnitrosourea. Proteins from the livers...

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Bibliographic Details
Published in:The Journal of biological chemistry 1987-09, Vol.262 (26), p.12764-12767
Main Authors: Giometti, C S, Gemmell, M A, Nance, S L, Tollaksen, S L, Taylor, J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Computers
DNA Damage
Electrophoresis, Polyacrylamide Gel
Ethylnitrosourea - pharmacology
Female
Gamma Rays
General aspects. Methods
Liver - analysis
Male
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL - genetics
Mutation
Proteins - genetics
Toxicology
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Summary:A computerized search for the appearance of heritable mutations (as indicated by changes in protein expression) was conducted on three sets of mice, whose sires had been either untreated, exposed to 3 gray units of gamma radiation, or treated with 150 mg/kg ethylnitrosourea. Proteins from the livers of approximately 800 mice were separated by two-dimensional electrophoresis, and abundances were measured by using image analysis techniques. Heritable mutations were detected by the appearance of new proteins or by the quantitative decrease in abundance of normally occurring proteins. Measurements of the variability of the protein abundance indicate that at least 48 proteins are consistent enough to be used in searches when mutations are expected to result in a 50% reduction in the normal amount of protein. New proteins were found in four offspring from ethylnitrosourea-treated mice, and in each case a nearby spot was found to be significantly diminished. These mutations were confirmed in subsequent generations. A computer-assisted search detected three of these mutations on the basis of the abundance decrease alone. These results indicate that two-dimensional electrophoresis can be used to detect mutations reflected as quantitative changes in protein expression, provided that the proteins to be monitored are quantitatively stable when samples from different individuals are compared.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)45272-6