Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Jan;85(1):180–184. doi: 10.1073/pnas.85.1.180

Saturation germ line mutagenesis of the murine t region including a lethal allele at the quaking locus.

A Shedlovsky 1, T R King 1, W F Dove 1
PMCID: PMC279507  PMID: 3422415

Abstract

The proximal region of mouse chromosome 17 contains many genes affecting embryonic development, germ cell differentiation, and the immune system. Although the study of natural variation, including t haplotypes, has yielded some information about the function of these genes, spontaneous variants often exhibit manifold genetic effects and are generally not carried on inbred backgrounds. To clearly connect phenotypes with the actions of individual genes, mutants in which genes are altered singly are needed. Therefore, we used a highly efficient point mutagen, N-ethyl-N-nitrosourea, in combination with classical breeding schemes to induce and identify recessive lethal mutations in the t region. Of 350 mutagenized gametes examined, at least 10 independent recessive embryonic lethal mutations have been identified; an additional two are perinatal lethals. A spontaneous brachyury mutation, TWis, arose on a genetic background that permits high-resolution mapping of the induced recessive mutations against cloned DNA sequences from the t region. One lethal mutation is an allele at the quaking locus. The multiple alleles of quaking and the feasibility of high-resolution mapping permit investigation of the pleiotropic action of this locus in mammalian development.

Full text

PDF
180

Images in this article

183Image
on p.183

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Artzt K., Babiarz B., Bennett D. A t-haplotype (tw75) overlapping two complementation groups. Genet Res. 1979 Jun;33(3):279–285. doi: 10.1017/s0016672300018425. [DOI] [PubMed] [Google Scholar]
  2. BAILEY D. W., USAMA B. A rapid method of grafting skin on tails of mice. Transplant Bull. 1960 Apr;7:424–425. doi: 10.1097/00006534-196004000-00045. [DOI] [PubMed] [Google Scholar]
  3. Bailey D. W., Kohn H. I. Inherited histocompatibility changes in progeny of irradiated and unirradiated inbred mice. Genet Res. 1965 Nov;6(3):330–340. doi: 10.1017/s0016672300004225. [DOI] [PubMed] [Google Scholar]
  4. Bechtol K. B. Lethality of heterozygotes between t-haplotype complementation groups of mouse: sex-related effect on lethality of t6/tw5 heterozygotes. Genet Res. 1982 Feb;39(1):79–84. doi: 10.1017/s0016672300020759. [DOI] [PubMed] [Google Scholar]
  5. Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bode V. C. Ethylnitrosourea mutagenesis and the isolation of mutant alleles for specific genes located in the T region of mouse chromosome 17. Genetics. 1984 Oct;108(2):457–470. doi: 10.1093/genetics/108.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cattanach B. M., Kirk M. Differential activity of maternally and paternally derived chromosome regions in mice. Nature. 1985 Jun 6;315(6019):496–498. doi: 10.1038/315496a0. [DOI] [PubMed] [Google Scholar]
  8. Dove W. F. Developmental molecular genetics of the mouse and its embryonal carcinoma. Cell Differ. 1984 Dec;15(2-4):205–213. doi: 10.1016/0045-6039(84)90076-9. [DOI] [PubMed] [Google Scholar]
  9. Dove W. F. Molecular genetics of Mus musculus: point mutagenesis and millimorgans. Genetics. 1987 May;116(1):5–8. doi: 10.1093/genetics/116.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gluecksohn-Waelsch S., Erickson R. P. The T-locus of the mouse: implications for mechanisms of development. Curr Top Dev Biol. 1970;5:281–316. doi: 10.1016/s0070-2153(08)60058-7. [DOI] [PubMed] [Google Scholar]
  11. Greenspan R. J., O'Brien M. C. Genetic analysis of mutations at the fused locus in the mouse. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4413–4417. doi: 10.1073/pnas.83.12.4413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Herrmann B., Bućan M., Mains P. E., Frischauf A. M., Silver L. M., Lehrach H. Genetic analysis of the proximal portion of the mouse t complex: evidence for a second inversion within t haplotypes. Cell. 1986 Feb 14;44(3):469–476. doi: 10.1016/0092-8674(86)90468-x. [DOI] [PubMed] [Google Scholar]
  13. Hood L., Steinmetz M., Malissen B. Genes of the major histocompatibility complex of the mouse. Annu Rev Immunol. 1983;1:529–568. doi: 10.1146/annurev.iy.01.040183.002525. [DOI] [PubMed] [Google Scholar]
  14. Johnson D. R. Further observations on the haipin-tail (Thp) mutation in the mouse. Genet Res. 1974 Oct;24(2):207–213. doi: 10.1017/s0016672300015226. [DOI] [PubMed] [Google Scholar]
  15. Justice M. J., Bode V. C. Induction of new mutations in a mouse t-haplotype using ethylnitrosourea mutagenesis. Genet Res. 1986 Jun;47(3):187–192. doi: 10.1017/s0016672300023119. [DOI] [PubMed] [Google Scholar]
  16. Klein J., Figueroa F., Nagy Z. A. Genetics of the major histocompatibility complex: the final act. Annu Rev Immunol. 1983;1:119–142. doi: 10.1146/annurev.iy.01.040183.001003. [DOI] [PubMed] [Google Scholar]
  17. Kuehn M. R., Bradley A., Robertson E. J., Evans M. J. A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature. 1987 Mar 19;326(6110):295–298. doi: 10.1038/326295a0. [DOI] [PubMed] [Google Scholar]
  18. Le Meur M., Gerlinger P., Benoist C., Mathis D. Correcting an immune-response deficiency by creating E alpha gene transgenic mice. Nature. 1985 Jul 4;316(6023):38–42. doi: 10.1038/316038a0. [DOI] [PubMed] [Google Scholar]
  19. Lyon M. F. Male sterility of the mouse t-complex is due to homozygosity of the distorter genes. Cell. 1986 Jan 31;44(2):357–363. doi: 10.1016/0092-8674(86)90770-1. [DOI] [PubMed] [Google Scholar]
  20. Mains P. E. The cis-trans test shows no evidence for a functional relationship between two mouse t complex lethal mutations: implications for the evolution of t haplotypes. Genetics. 1986 Dec;114(4):1225–1237. doi: 10.1093/genetics/114.4.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mann E. A., Silver L. M., Elliott R. W. Genetic analysis of a mouse t complex locus that is homologous to a kidney cDNA clone. Genetics. 1986 Nov;114(3):993–1006. doi: 10.1093/genetics/114.3.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McGrath J., Solter D. Maternal Thp lethality in the mouse is a nuclear, not cytoplasmic, defect. Nature. 1984 Apr 5;308(5959):550–551. doi: 10.1038/308550a0. [DOI] [PubMed] [Google Scholar]
  23. Murphy D. B., Shrefler D. C. Cross-reactivity between H-2K and H-2D products. I. Evidence for extensive and reciprocal serological cross-reactivity. J Exp Med. 1975 Feb 1;141(2):374–391. doi: 10.1084/jem.141.2.374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Readhead C., Popko B., Takahashi N., Shine H. D., Saavedra R. A., Sidman R. L., Hood L. Expression of a myelin basic protein gene in transgenic shiverer mice: correction of the dysmyelinating phenotype. Cell. 1987 Feb 27;48(4):703–712. doi: 10.1016/0092-8674(87)90248-0. [DOI] [PubMed] [Google Scholar]
  25. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  26. Rinchik E. M., Russell L. B., Copeland N. G., Jenkins N. A. Molecular genetic analysis of the dilute-short ear (d-se) region of the mouse. Genetics. 1986 Feb;112(2):321–342. doi: 10.1093/genetics/112.2.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Russell E. S. A history of mouse genetics. Annu Rev Genet. 1985;19:1–28. doi: 10.1146/annurev.ge.19.120185.000245. [DOI] [PubMed] [Google Scholar]
  28. Russell W. L., Kelly E. M., Hunsicker P. R., Bangham J. W., Maddux S. C., Phipps E. L. Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5818–5819. doi: 10.1073/pnas.76.11.5818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shedlovsky A., Guenet J. L., Johnson L. L., Dove W. F. Induction of recessive lethal mutations in the T/t-H-2 region of the mouse genome by a point mutagen. Genet Res. 1986 Apr;47(2):135–142. doi: 10.1017/s0016672300022977. [DOI] [PubMed] [Google Scholar]
  30. Silver L. M. Mouse t haplotypes. Annu Rev Genet. 1985;19:179–208. doi: 10.1146/annurev.ge.19.120185.001143. [DOI] [PubMed] [Google Scholar]
  31. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  32. Uehara H., Abe K., Park C. H., Shin H. S., Bennett D., Artzt K. The molecular organization of the H-2K region of two t-haplotypes: implications for the evolution of genetic diversity. EMBO J. 1987 Jan;6(1):83–90. doi: 10.1002/j.1460-2075.1987.tb04722.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Washburn L. L., Eicher E. M. Sex reversal in XY mice caused by dominant mutation on chromosome 17. Nature. 1983 May 26;303(5915):338–340. doi: 10.1038/303338a0. [DOI] [PubMed] [Google Scholar]
  34. Willison K. R., Dudley K., Potter J. Molecular cloning and sequence analysis of a haploid expressed gene encoding t complex polypeptide 1. Cell. 1986 Mar 14;44(5):727–738. doi: 10.1016/0092-8674(86)90839-1. [DOI] [PubMed] [Google Scholar]
  35. Winking H., Silver L. M. Characterization of a recombinant mouse T haplotype that expresses a dominant lethal maternal effect. Genetics. 1984 Dec;108(4):1013–1020. doi: 10.1093/genetics/108.4.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES