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Induction of recessive lethal mutations in the T/tH-2 region of the mouse genome by a point mutagen1

Published online by Cambridge University Press:  14 April 2009

Alexandra Shedlovsky
Affiliation:
McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin, Madison, W1 53706U.S.A.
Jean-Louis Guenet
Affiliation:
Génétique des Mammifères, Institut Pasteur, 25, rue du Docteur Roux, 75015 Paris, France
Lawrence L. Johnson
Affiliation:
McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin, Madison, W1 53706U.S.A.
William F. Dove
Affiliation:
McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin, Madison, W1 53706U.S.A.
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Summary

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The T/tH-2 region on mouse chromosome 17 is known from complex natural variants (‘t-haplotypes’) to contain numerous genes, including some affecting the immune system and the development of the embryo. Rapid progress in the isolation of recombinant DNA clones for this 50 megabasepair region is generating the material for its complete molecular anatomy. A crucial step in revealing the biological functions controlled by the region is to obtain mutants in which genes are inactivated individually. We have used a pair of inbred mouse strains and a series of classical breeding schemes that permit the detection of recessive lethal and detrimental mutations in the T/tH-2 region.

In this initial phase of our study, 280 gametes mutagenized in the male germ line by ethylnitrosourea (ENU) have yielded eleven independent pre-natal recessive lethal mutations. Four have been mapped against T mutations and have been shown to complement one another in all pairwise combinations.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1986

References

Alton, A. K., Silver, L. M., Artzt, K. & Bennett, D. (1980). Genetic relationship of trans interacting factors at the T/t complex: a molecular analysis. Nature 228, 368370.Google Scholar
Artzt, K., McCormick, P. & Bennett, D. (1982). Gene mapping within the T/t complex of the mouse. I. t-lethal genes are nonallelic. Cell 28, 463470.Google Scholar
Babiarz, B., Garrisi, G. J. & Bennett, D. (1982). Genetic analysis of the tw73 haplotype of the mouse using deletion mutations: evidence of a parasitic lethal mutation. Genetical Research 39, 111120.Google Scholar
Bailey, D. W. & Kohn, H. I. (1965). Inherited histocompatibility changes in progeny of irradiated and unirradiated inbred mice. Genetical Research 6, 330340.CrossRefGoogle ScholarPubMed
Bennett, D. (1975). The T-locus of the mouse. Cell 6, 441454.Google Scholar
Bennett, D. (1980). The T-complex in the mouse: an assessment after 50 years of study. The Harvey Lectures 74, 121.Google ScholarPubMed
Bode, V. C. (1984). Ethylnitrosourea mutagenesis and the isolation of mutant alleles for specific genes located in the T region of mouse chromosome 17. Genetics 108, 457470.Google Scholar
Carter, T. C. (1957). Recessive lethal mutations induced in the house mouse by chronic X-irradiation. Proceedings of the Royal Society B 147, 402411.Google Scholar
Chada, K., Magram, J., Raphael, K., Radice, G., Lacy, E. & Constantini, F. (1985). Specific expression of a foreign β-globin gene in erythroid cells of transgenic mice. Nature 314, 377380.Google Scholar
Dove, W. F. (1984). Developmental molecular genetics of the mouse and its embryonal carcinoma. Cell Differentiation 15, 205213.Google Scholar
Ehling, U. H. & Neuhäuser-Klaus, A. (1984). Dose effect relationships of germ-cell mutations in mice. In Problems of Threshold in Chemical Mutagenesis (ed. Tazina, Y. et al. ). The Environmental Mutagen Society of Japan.Google Scholar
Erickson, R. P., Lewis, S. E. & Slusser, K. S. (1978). Deletion mapping of the t complex of chromosome 17 of the mouse. Nature 274, 163164.CrossRefGoogle Scholar
Fox, H. S., Martin, G. R., Lyon, M. F., Herrmann, B., Fischauf, A. M., Lehrach, H. & Silver, L. M. (1985). Molecular probes define different regions of the mouse t complex. Cell 40, 6369.CrossRefGoogle ScholarPubMed
Gluecksohn-Waelsch, S. & Erickson, R. P. (1970). The T locus of the mouse: Implications for mechanisms of development. Current Topics in Developmental Biology 5, 281316.Google Scholar
Haldane, J. B. S. (1956). The detection of autosomal lethals in mice induced by mutagenic agents. Journal of Genetics 54, 327342.Google Scholar
Jenkins, N. & Copeland, N. (1985). High frequency germline acquisition of ecotropic MuLV proviruses in SWR/J-RF/J hybrid mice. Cell (In the Press.)Google Scholar
Johnson, D. R. (1974). Hairpin-tail. A case of post-reductional gene action in the mouse egg. Genetics 76, 795805.CrossRefGoogle ScholarPubMed
Johnson, F. M. & Lewis, S. E. (1981). Electrophoretically detected germinal mutations induced in the mouse by ethylnitrosourea. Proceedings of the National Academy of Sciences U.S.A. 78, 31383141.CrossRefGoogle ScholarPubMed
Justice, M. & Bode, V. C. (1986). Isolation of new mutations in t-chromatin using ethylnitrosourea. Genetical Research (In the Press.)Google Scholar
Kataoka, T., Powers, S., McGill, C., Fasano, O., Strathern, J., Broach, J. & Wigler, M. (1984). Genetic Analysis of Yeast RAS1 and RAS2 Genes. Cell 37, 437445.CrossRefGoogle ScholarPubMed
Klein, J. & Hammerberg, C. (1977). Thecontrol of differentiation by the T complex. Immunological Reviews 33, 70104.CrossRefGoogle Scholar
Lawley, P. D. & Shah, S. A. (1972). Methylation of Ribonucleic Acid by the Carcinogens Dimethyl Sulphate, N Methyl-N-Nitrosourea and N-Methyl-N'-nitro-N-nitrosoguanidine. Biochemical Journal 128, 117132.Google Scholar
Le Meur, M., Gerlinger, P., Bnoist, C. & Mathis, D. (1985). Correcting an immune-response deficiency by creating E α gene transgenic mice. Nature 316, 3842.CrossRefGoogle Scholar
Lüning, K. G. & Searle, A. G. (1971). Estimates of genetic risks from ionizing irradiation. Mutation Research 12, 291304.Google Scholar
Lyon, M. F. (1959). Some evidence concerning ‘mutational load’ in inbred strains of mice. Heredity 13, 341352.Google Scholar
Lyon, M. F., Evans, E. P., Jarvis, S. E. & Sayers, I. (1979). t-Haplotypes of the mouse may involve a change in intercalary DNA. Nature 279, 3842.CrossRefGoogle ScholarPubMed
Muller, H. J. & Altenberg, E. (1919). The rate of change of hereditary factors in Drosophila. Proceedings of the Society of Experimental Biology and Medicine 17, 1014.Google Scholar
Murphy, D. B. & Shreffler, D. C. (1975). Cross-reactivity between H-2K and H-2D products. Journal of Experimental Medicine 141, 374391.Google Scholar
Popp, R. A., Bailiff, E. G., Skow, L. C., Johnson, F. M. & Lewis, S. E. (1983). Analysis of a mouse α-globin gene mutation induced by ethylnitrosourea. Genetics 105, 157167.CrossRefGoogle ScholarPubMed
Russell, W. L., Kelly, E. M., Hunsicker, P. R., Bangham, J. W., Maddux, S. C. & Phipps, E. L. (1979). Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. Proceedings of the National Academy of Sciences, U.S.A. 76. 58185819.Google Scholar
Russell, W. L., Hunsicker, P. R., Raymer, G. D., Steele, M. H., Stelzner, K. F. & Thompson, H. M. (1982). Dose response for ethylnitrosourea-induced-specific-locus mutations in mouse spermatogonia. Proceedings of the National Academy of Sciences U.S.A. 79, 35893591.Google Scholar
Schnieke, A., Harbers, K. & Jaenisch, R. (1983). Embryonic lethal mutation in mice induced by retrovirus insertion into the α l(I) collagen gene. Nature 304, 315320.Google Scholar
Sherman, M. I. & Wudl, L. D. (1977). T-complex mutations and their effects. In Concepts in Mammalian Embryogenesis (ed. Sherman, M. I.) pp. 136234. Cambridge, Mass: M.I.T. Press.Google Scholar
Shin, H.-S., McCormick, P., Artzt, K. & Bennett, D. (1983). Cis-trans test shows a functional relationship between non-allelic lethal mutations in the T/t complex. Cell 33, 925929.Google Scholar
Snell, G. D. (1935). The induction by X-rays of hereditary changes in mice. Generics 20, 545567.Google Scholar
Silver, L. M. (1986). Mouse t haplotypes. Annual Review of Genetics 19, 179208.Google Scholar
Silver, L. M. & Artzt, K. (1981). Recombination suppression of mouse t-haplotypes due to chromatin mismatching. Nature 290, 6870.CrossRefGoogle ScholarPubMed
Steinmetz, M. & Hood, L. (1983). Genes of the major histocompatibility complex in mouse and man. Science 222, 727733.Google Scholar
Storr, U., O'Brien, R. L., McMullen, M. D., Gollahon, K. A. & Brinster, R. L. (1984). High expression of cloned immunoglobulin K gene in transgenic mice is restricted to B lymphocytes. Nature 310, 238241.Google Scholar
Tatchell, K., Chaleff, D., Defeo-Jones, D. & Scolnick, E. (1984). Requirement of either of a pair of ras-related genes of Saccharomyces cerevisiae for spore viability. Nature 309, 523527.Google Scholar
van der Putten, H., Botteri, F. M., Miller, A. D., Rosenfeld, M. G., Fan, H., Evans, R. M. & Verma, I. M. (1985). Efficient insertion of genes into the mouse germline via retroviral vectors. Proceedings of the National Academy of Sciences U.S.A. 82, 61486152.Google Scholar
Vogel, E. & Natarjan, A. T. (1979). The relation between reaction kinetics and mutagenic action of mono-functional alkylating agents in higher eukaryotic systems. I. Recessive lethal mutations and translocations in drosophila. Mutational Research 62, 51100.Google Scholar
Wallis, J. W., Rykowski, M. & Grunstein, M. (1983). Yeast histone H2B containing large amino terminus deletions can function in vivo. Cell 35, 711719.Google Scholar
Yamamura, K., Kikutani, H., Folsom, V., Clayton, L. K., Kimoto, M., Akira, S., Kashiwamura, S., Tonegawa, S. & Kishimoto, T. (1985). Functional expression of a microinjected gene in C57BL/6 transgenic mice. Nature 316, 6769.CrossRefGoogle ScholarPubMed