Hostname: page-component-76fb5796d-5g6vh Total loading time: 0 Render date: 2024-04-25T23:45:49.269Z Has data issue: false hasContentIssue false

Induction of new mutations in a mouse t-haplotype using ethylnitrosourea mutagenesis

Published online by Cambridge University Press:  14 April 2009

Monica J. Justice
Affiliation:
Division of Biology, Ackert Hall, Kansas State University, Manhattan, Kansas 66506, U.S.A.
Vernon C. Bode
Affiliation:
Division of Biology, Ackert Hall, Kansas State University, Manhattan, Kansas 66506, U.S.A.
Rights & Permissions [Opens in a new window]

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

N-ethyl-N-nitrosourea (ENU) was used to induce mutations within the tw5-haplotype of the mouse to make possible a further study of gene arrangement in t-mutants and to provide potential landmarks for cloning and sequence studies in the region. Two independent mutants were isolated for each of three loci in the t-region, brachyury (T), quaking (qk), and tufted (tf). The new Tkt alleles produce tailless mice when a tct mutation is present in trans. The new qkkt alleles are recessive and homozygous lethal. They are viable, male fertile, and cause seizures and quaking when paired with the qk mutation which previously defined the locus. The tfkt mutations are recessive and phenotypically similar to the mutant alleles available in non-t chromosomes. The mutations were induced in the tw5-haplotype at an average per locus frequency of 1 in 1500. Their isolation demonstrates the power of this technique for obtaining the specific mouse mutants that are needed to genetically dissect a complex mammalian system.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1986

References

Artzt, K. (1984). Gene mapping within the T/t complex of the mouse. III. t-lethal genes are arranged in three clusters on chromosome 17. Cell 39, 565572.CrossRefGoogle Scholar
Artzt, K., McCormick, P. & Bennett, D. (1982 a). Gene mapping within the T/t complex of the mouse. 1. t-Lethal genes are nonallelic. Cell 28, 463470.CrossRefGoogle Scholar
Artzt, K., Shin, H.-S. & Bennett, D. (1982 b). Gene mapping within the T/t complex of the mouse. II. Anomalous position of H-2 complex in t-haplotypes. Cell 28, 471476.CrossRefGoogle Scholar
Bennett, D. (1975). The t-locus of the mouse. Cell 6, 441454.CrossRefGoogle Scholar
Bennett, W., Gall, A. M., Southard, J. L. & Sidman, R. L. (1971). Abnormal spermiogenesis in quaking, a myelin deficient mutant mouse. Biology of Reproduction 5, 3058.CrossRefGoogle 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.CrossRefGoogle Scholar
Condamine, H., Guenet, J.-L. & Jacob, F. (1983). Recombination between two mouse t-haplotypes (tw12tf and tLub-l): segregation of lethal factors relative to centromere and tufted (tf) locus. Genetical Research 42, 335344.CrossRefGoogle ScholarPubMed
Forejt, J., Capkona, J. & Gregorova, S. (1980). T(16: 17)34H translocation as a tool in analysis of the proximal part of chromosome 17 (including T-t gene complex) of the mouse. Genetical Research 35, 165177.CrossRefGoogle Scholar
Fox, H. S., Martin, G. R., Lyon, M. F., Hermann, B., Frischauf, A. -M., Lerach, H. & Silver, L. M. (1985). Molecular probes define different regions of the mouse t-complex. Cell 40, 6369.CrossRefGoogle ScholarPubMed
Hitotsumachi, S., Carpenter, D. A. & Russell, W. L. (1983). Dose fractionation as a means of increasing the mutagenic effectiveness of ethylnitrosourea in mouse spermatogonia. Environmental Mutagen 5, 380.Google Scholar
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
Klein, J. & Hammerberg, C. (1977). The control of differentiation by the T complex. Immunological Reviews 33, 70104.CrossRefGoogle ScholarPubMed
Lyon, M. F. (1981). The t-complex and the genetic control of development. In Biology of the House Mouse (ed, Berry, R. J.). London: Academic Press.Google Scholar
Lyon, M. F. (1984). Transmission ratio distortion in mouse t-haplotypes is due to multiple distorter genes acting on a responder locus. Cell 37, 621628.CrossRefGoogle ScholarPubMed
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
Nadeau, J. H., Phillips, S. J. & Egorov, I. K. (1985). Recombination between the t 6 complex and linked loci in the house mouse. Genetical Research 45, 251264.CrossRefGoogle ScholarPubMed
Peters, J. (1983). Some characterizations of mutations induced by ENU in the mouse. Hereditas 98, 158.Google Scholar
Peters, J., Andrews, S. J., Ball, S. T., Loutit, J. F. & Glegg, J. B. (1985). Induction of mutants by ethylnitrosourea and their analysis. Hereditas (In the Press).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
Rogers, J. H. & Willison, K. R. (1983). A major rearrangement in the H-2 complex of mouse t haplotypes. Nature 304, 549552.CrossRefGoogle Scholar
Rohme, D., Fox, H., Herrmann, B., Frischauf, A.-M., Edstrom, J.-E., Mains, F., Silver, L. M. & Lehrach, H. (1984). Molecular clones of the mouse t complex derived from microdissected metaphase chromosomes. Cell 36, 783788.CrossRefGoogle Scholar
Russell, W. L., Hunsicker, P. R., Carpenter, D. A., Cornett, C. V. & Guinn, G. M. (1982 a). Effect of dose fractionation on the ethylnitrosourea induction of specific-locus mutations in mouse spermatogonia. Proceedings of the National Academy of Sciences, U.S.A. 79, 35923593.CrossRefGoogle ScholarPubMed
Russell, W. L., Hunsicker, P. R., Raymer, G. D., Steele, M. H., Stelzner, K. F. and Thompson, H. M. (1982 b). Dose response curve for ethylnitrosourea-induced specific-locus mutations in mouse spermatogonia. Proceedings of the National Academy of Sciences, U.S.A. 79, 35893591.CrossRefGoogle ScholarPubMed
Russell, W. L., Kelly, E. M., Hunsicker, P. R., Bangham, J. W., Maddux, 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.CrossRefGoogle ScholarPubMed
Sherman, M. I. & Wudl, L. R. (1977). T-complex mutations and their effects. In Concepts in Embryogenesis (ed. Sherman, M. I.). Cambridge: MIT Press.Google Scholar
Shin, H. -S., Bennett, D. & Artzt, K. (1984). Gene mapping within the T/t complex of the mouse. IV. The inverted MHC is intermingled with several t-lethal genes. Cell 39, 573578.CrossRefGoogle Scholar
Shin, H. -S., Flaherty, L., Artzt, K., Bennett, D. & Ravetch, J. (1983). Inversion in the H-2 complex of t-haplotypes in mice. Nature 306, 360383.CrossRefGoogle ScholarPubMed
Silver, L. M. (1981). A structural gene (Tcp-1) within the mouse t complex is separable from effects on tail length and lethality but may be associated with effects on spermatogenesis. Genetical Research 38, 115123.CrossRefGoogle Scholar
Silver, L. M. (1982). Genomic analysis of the H-2 complex region associated with mouse t haplotypes. Cell 29, 961968.CrossRefGoogle ScholarPubMed
Silver, L. M. & Artzt, K. (1981). Recombination suppression of mouse t-haplotypes due to chromatin mismatching. Nature 290, 6870.CrossRefGoogle ScholarPubMed
Silver, L. M., Lukralle, D. & Garrels, J. I. (1983 a). T orl is a novel, variant form of mouse chromosome 17 with a deletion in a partial t-haplotype. Nature 301, 422424.CrossRefGoogle Scholar
Silver, L. M., Uman, J., Danska, J. & Garrels, J. I. (1983 b). A diversified set of testicular cell proteins specified by genes within the mouse t-complex. Cell 35, 3545.CrossRefGoogle ScholarPubMed
Vogel, E. & Natarjan, A. T. (1979). The relation between reaction kinetics and mutagenic action of mono-functional alkylating agents in higher eukaryotic systems. 1. Recessive lethal mutations and translocations in Drosophila. Mutation Research 62, 51100.CrossRefGoogle ScholarPubMed