Specific locus test

Because the occurrence of mutation is rare even after mutagen treatment, the specific locus test is the ultimate study of mutation, requiring many thousands of offspring to be scored, plus significant resources of time, space, and animal... 

Searle, A.G. (1984). The specific locus test in the mouse. In Handbook of Mutagenicity Test Procedures (Kilbey, B.J., Legator, M., Nichols, W. and Ramel, C., Eds.). Elsevier, Amsterdam, pp. 373-391. 

Mouse biochemical specific locus test (August 1998)... 

The Mouse Visible Specific Locus Test (MSLT)... 

Positive results in the Mouse Biochemical Specific Locus Test (MBSL) and/or in the Mouse Visible Specific Locus Test (MSLT) indicate that the test substance induces heritable gene mutations in a mammahan species. 

MBSL Mouse Biochemical Specific Locus Test... 

Russell, L.B., Selby, P.B., von Halle, E., Sheridan, W. and Valcovic, L. The mouse specific-locus test with agents other than radiations Interpretation of data and recommendations for future work. Mutat. Res. 86 329-354, 1981. 

Russell, L.B., Hunsicker, PR. Cacheiro, N.L.A. (1986) Mouse specific-locus test for the induc-... 

Barnett, L.B., Lovell, D.P.., Felton, C.F., Gibson, B.J., Cobb, R.R., Sharpe, D.S., Shelby, M.D. Lewis, S.E. (1992) Ethylene dibromide negative results with the mouse dominant lethal asssay and the electrophoretic specific locus test. Mutat. Res., 282, 127-133... 

SLP, Mouse specific locus test, (101/El x C3H E1)I mice. (+) 200 ip X 1 Ehling Neuhauser-Klaus... 

The gene mutation test systems in mice include the specific locus test, in which wild-type treated males are crossed with females carrying recessive mutations for visible phenotypic effects. The F progeny have the same phenotype as the wild-type parent unless a mutation, corresponding to a recessive mutant marker, has occurred. Such tests... 

If a decision still cannot be reached reliably in Level 3, a mammalian test (Level 4) is recommended. If the expected effect is chromosomal, a dominant-lethal test is appropriate. If the expected effect is genic, then the specific-locus test is appropriate. A positive result in either test is sufficient to classify a chemical as a mammalian mutagen, regardless of the results of short-term tests. However, the dominant-lethal test may sometimes detect effects that are nongenetic. 

Mammals Mutation Mouse Specific-locus test... 

A recently developed version of the specific-locus test detects electrophoretic protein variants at at least 21 loci.101 198 It is based on early test-system development by Mailing and Valcovic270 and Soares.1+24 A significant increase in the mutation frequency for ENU has been demonstrated with this test. 95 Two inbred strains of mice are used that differ at 10 loci whose protein products are electrophoretically demonstrable. In addition, mutations resulting in the loss of any of 11 other proteins common to the two strains can be detected. Males of either strain are exposed to the test substance, and, at the desired time after exposure, they are mated with females of the other strain. Later, all parental and Fi animals are examined for the biochemical characters of interest. 

There are many possible ways in which mammalian tests can be combined to yield more information per mouse. For example, if one is willing to decrease the rate at which offspring are evaluated in specific-locus tests, the same offspring can be observed for cataracts or other effects. The dominant-cataract-mutation test, in its present form, is done in this way.221 Also, male parents used for dominant-lethal tests on postspermatogonial stages can be used for other tests on spermatogonia. 

The specific-locus test is not intended for human risk estimation. The seven loci sampled may not be representative of the whole genome. To continue the example of the appendix to this chapter, a mutation rate of 0.000003 per seven loci corresponds to 0.009 for 20,000 loci, if this is taken as the haploid gene number. This is nearly 1% per zygote, not a negligible number. It would be desirable to have methods to measure mutations in the entire genome, or in an entire chromosome, such as are used in Drosophila. Such methods are being developed in mice, but cure not yet suitable for routine use. 

TABLE 6-2 Comparison of the Results of 17 Compounds Tested in Both the Mouse Specific-Locus Test and the Drosophila X-linked Lethal Testa... 

Nine chemicals are shown for the specific-locus test. 

If the previous tests do not suffice for a decision, further testing in mammals is indicated. If the purpose is to get mammalian germinal data on whether a substance produces mutations, the specific-locus test is suitable because of its low background rate and the extent to which the test has been performed. It should be recognized, however, that chemicals that yield inconclusive results in short-term tests are likely to yield negative or inconclusive results in mouse tests. The dominant-lethal test may be used if the expected effect is chromosomal. 

Russell, W.L. Factors affecting mutagenicity of ethylnitrosourea in the mouse specific-locus test and their bearing on risk estimation, pp. 59-70. In... 

Russell, W.L., E.M. Kelly, P.R. Hunsicker, J.W. Bangham, S.C. Maddux, and E.L. Phipps. Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. Proc. Natl. Acad. Sci. U.S.A. 76 5818-5819, 1979. 

A few examples include the mouse specific-locus test for germ-cell mutagenesis (Russell 1994 Russell 1989), tests for forward and reverse mutations in the ad-3 region of Neurospora crassa (de Serres and Kolmark 1958), the Tradescantia stamen-hair system (Underbrink et al. 1973), and the rlllocus test for bacteriophage T4 (Drake 1963). Many others could be noted. 

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