Biochemical Genetics

, Volume 25, Issue 5–6, pp 401–413 | Cite as

The aryl hydrocarbon hydroxylase (Ah) locus and a novel restriction-fragment length polymorphism (RFLP) are located on mouse chromosome 12

  • Ronald R. Cobb
  • Terrance A. Stoming
  • J. Barry WhitneyIII
Article

Abstract

The aryl hydrocarbon hydroxylase (Ah) locus that controls the induction of chemical carcinogen-metabolizing enzymes in mice has been found to be linked to a new restriction-fragment length polymorphism (RFLP). Only C57 BL/6 and closely related inbred strains displayed a 7.6-kbHindIII restriction fragment, while all other inbred strains tested displayed an 11.2-kbHindIII restriction fragment when using plasmid pRC2.3 as the hybridization probe. Polymorphisms in this region can also be detected with two other restriction enzymes:SacI andEcoRV. Linkage ofAh and the restriction-fragment length polymorphism was first detected using the BXD (C57BL/6 × DBA/2) recombinant inbred strains and was confirmed by a backcross. Both the restriction-fragment length polymorphism andAh were not linked to the standard genetic markersHba, Hbb, b, d, C-3, andW. However, comparison of the RFLP strain distribution pattern in the BXD recombinant inbred set with the strain distribution pattern of another RFLP, known to be located on chromosome 12, shows complete concordance in 24 of 24 strains, thereby locatingAh on chromosome 12.

Key words

mammalian genetics gene mapping Mus musculus carcinogenesis 

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References

  1. Cobb, R. R., and Whitney, J. B., III (1984). Restriction fragment length polymorphism found associated with the Ah locus.Genetics 107:s21.Google Scholar
  2. Dagert, M., and Ehrlich, S. D. (1979). Prolonged incubation in calcium chloride improves the competence ofEscherichia coli cells.Gene 623.Google Scholar
  3. D'Eustachio, P. (1984). A genetic map of mouse chromosome 12 composed of polymorphic DNA fragments.J. Exp. Med. 160827.Google Scholar
  4. Gielen, J. E., Goujon, F. M., and Nebert, D. W. (1972). Genetic regulation of aryl hydrocarbon hydroxylase induction: Simple Mendelian expression in mouse tissuesin vivo.J. Biol. Chem. 2471125.Google Scholar
  5. Goodbourn, S. E. Y., Higgs, D. R., Clegg, J. R., and Weatherall, D. J. (1983). Molecular basis of length polymorphism in the human ζ-globin complex.Proc. Natl. Acad. Sci. USA 805022.Google Scholar
  6. Guenthner, T. M., an Nebert, D. W. (1977). Cytosolic receptor for aryl hydrocarbon hydroxylase induction by polycyclic aromatic compounds: Evidence for structural and regulatory variants among established cell culture lines.J. Biol. Chem. 2528981.Google Scholar
  7. Ish-Horowicz, D., and Burke, J. F. (1981). Rapid and efficient cosmid cloning.Nucleic Acids Res. 92989.Google Scholar
  8. Jenkins, N. A., Copeland, N. G., Taylor, B. A., and Lee, B. K. (1981). Dilute (d) coat color mutation of DBA/2J is associated with the site of integration of an ecotropic MuLV genome.Nature 293370.Google Scholar
  9. Lang, M. A., Gielen, J. E., and Nebert, D. W. (1981). Genetic evidence for many unique liver microsomal P-450-mediated monooxgenase activities in heterogeneic stock mice.J. Biol. Chem. 25612068.Google Scholar
  10. Leder, A., Swan, D., Ruddle, F., D'Eustachio, P., and Leder, P. (1981). Dispersion of α-like globin genes of the mouse to three different chromosomes.Nature 293199.Google Scholar
  11. Leder, A., Weir, L., and Leder, P. (1985). Characterization, expression and evolution of the mouse embryonic ξ-globin gene.Mol. Cell. Biol. 51025.Google Scholar
  12. Legraverend, C., Karenlampi, S. O., Bigelow, S. W., Lalley, P. A., Kozak, C. A., Womack, J. E., and Nebert, D. W. (1984). Aryl hydrocarbon hydroxylase induction by benzo(a)anthrene: Regulatory gene localized to the distal portion of mouse chromosome 17.Genetics 107447.Google Scholar
  13. Maniatis, T., Fritsch, E. F., and Sambrook, J. (1982).Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.Google Scholar
  14. Nebert, D. W., Negishi, M., Lang, M. A., Hjelmeland, L. M., and Eisen, H. J. (1972). TheAh locus, a multigene family necessary for survival in a chemically adverse environment: Comparison with the immune system.Adv. Genet. 211.Google Scholar
  15. Nebert, D. W., Robinson, J. R., Niwa, A., Kumaki, K., and Poland, A. (1975). Genetic expression of aryl hydrocarbon hydroxylase activity in the mouse.J. Cell. Physiol. 85393.Google Scholar
  16. Nebert, D. W., Eisen, H. J., Negishi, M., Lang, M. A., Hjelmeland, L. M., and Okey, A. B. (1981). Genetic mechanisms controlling the induction of polysubstrate monooxgenase (P-450) activities.Annu. Rev. Pharmacol. Toxicol. 21431.Google Scholar
  17. Nebert, D. W., Jensen, N. M., Shinozuka, H., Kunz, H. W., and Gill, T. J., III (1982). TheAh phenotype. Survey of forty-eight rat strains and twenty inbred mouse strains.Genetics 10079.Google Scholar
  18. Nebert, D. W., Brown, D. D., Towne, D. W., and Eisen, H. J. (1984). Association of fertility, fitness, and longevity with murineAh locus among (C57BL/6N) (C3H/HeN) recombinant inbred lines.Biol. Reprod. 30363.Google Scholar
  19. Negishi, M., and Nebert, D. W. (1981). Structural gene products of theAh complex: Increases in large mRNA from mouse liver associated with cytochrome P1-450 induction by 3-methylcholanthrene.J. Biol. Chem. 2563085.Google Scholar
  20. Ohyama, T., Nebert, D. W., and Negishi, M. (1984). Isosafrole-induced cytochrome P2-450 in DBA/2N mouse liver.J. Biol. Chem. 2592675.Google Scholar
  21. Okey, A. B., Bondy, G. P., Mason, M. E., Kahl, G. F., Eisen, H. J., Guenthner, T. M., and Nebert, D. W. (1979). Regulatory gene products of theAh locus: characterization of the cytosolic inducer-receptor complex and evidence for its nuclear translocation.J. Biol. Chem. 25411636.Google Scholar
  22. Okey, A. B., Bondy, G. P., Mason, M. E., Nebert, D. W. Forster-Gibson, C. J., Muncan, J., and Dufresne, M. J. (1980). Temperature-dependent cytosol-to-nucleus translocation of theAh receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in continuous cell culture lines.J. Biol. Chem. 25511415.Google Scholar
  23. Poland, A. P., Glover, E., Robinson, J. R., and Nebert, D. W. (1974). Genetic expression of aryl hydrocarbon hydroxylase activity. Induction of monooxygenase activities and cytochrome P1-450 formation by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice genetically “nonresponsive” to other hydrocarbons.J. Biol. Chem. 2495599.Google Scholar
  24. Poland, A., Glover, E., and Kende, A. S. (1976). Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol: Evidence that the binding species is receptor for induction for aryl hydrocarbon hydroxylase.J. Biol. Chem. 2514936.Google Scholar
  25. Rigby, P. W. J., Diekmann, M., Rhodes, C., and Berg, P. (1977). Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase.J. Mol. Biol. 113237.Google Scholar
  26. Robinson, J. R., and Nebert, D. W. (1974). Genetic expression of aryl hydrocarbon induction: Presence or absence of association with zoxazolamine, diphenylhydantoin, and hexobarbital metabolism.Mol. Pharmacol. 10484.Google Scholar
  27. Robinson, J. R., Considine, N., and Nebert, D. W. (1974). Genetic expression of aryl hydrocarbon induction: Evidence for the involvement of other genetic loci.J. Biol. Chem. 2495855.Google Scholar
  28. Shichi, H., Gaasterland, D. E., Jensen, N. M., and Nebert, D. W. (1978).Ah locus: Genetic differences in susceptibility to cataracts induced by acetaminophen.Science 200539.Google Scholar
  29. Silvers, W. K. (1979).The Coat Colors of Mice: A Model for Mammalian Gene Action and Interaction Springer-Verlag, New York.Google Scholar
  30. Southern, E. M. (1975). Detection of specific sequences among DNA fragments separated by gel electrophoresis.J. Mol. Biol. 98503.Google Scholar
  31. Taylor, B. A. (1978). In Morse, H. C., III (ed.),Origins of Inbred Mice Academic Press, New York, pp. 447–461.Google Scholar
  32. Thorgieirsson, S. S., and Nebert, D. W. (1977). TheAh locus and the metabolism of chemical carcinogens and other foreign compounds.Adv. Cancer Res. 25149.Google Scholar
  33. Tukey, R. H., Hannah, R. R., Negishi, M., Nebert, D. W., and Eisen, H. J. (1982). TheAh locus: Correlation of intranuclear appearance of inducer-receptor complex with induction of cytochrome P1-450 mRNA.Cell 31275.Google Scholar
  34. Whitler, J. P., Jr., and Galeazzi, D. R. (1984). 2,3,7,8-Tetrachlorodibenzo-p-dioxin receptors in wild type and variant mouse hepatoma cells: Nuclear location and strength of nuclear binding.J. Biol. Chem. 259980.Google Scholar
  35. Whitney, J. B., III (1978). Simplified typing of mouse hemoglobin (Hbb) phenotypes using cystamine.Biochem. Genet. 16667.Google Scholar
  36. Whitney, J. B., III, Martinell, J., Popp, R. A., Russell, L. B., and Anderson, W. F. (1981). Deletions in the α-globin gene complex in α-thalassemic mice.Proc. Natl. Acad. Sci. USA 787644.Google Scholar
  37. Whitney, J. B., III, Cobb, R. R., Popp, R. A., and O'Rourke, T. W. (1985). Detection of neutral amino acid substitutions in proteins.Proc. Natl. Acad. Sci. USA 827646.Google Scholar

Copyright information

© Plenum Publishing Corporation 1987

Authors and Affiliations

  • Ronald R. Cobb
    • 1
  • Terrance A. Stoming
    • 1
  • J. Barry WhitneyIII
    • 1
  1. 1.Department of Cell and Molecular BiologyMedical College of GeorgiaAugusta

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