Skip to main content
Log in

Physical analysis of murine albino deletions that disrupt liver-specific gene regulation or mesoderm development

  • Original Contributions
  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

Complementation analyses of radiation-induced deletion mutations involving the albino (c) locus in Chromosome (Chr) 7 of the mouse have identified several loci, in addition toc, that have important roles in development. The “mesoderm-deficient” (msd) and “hepatocyte-specific developmental regulation-1” (hsdr-1) loci, which are proximal and tightly linked toc, are important in the formation of mesoderm and in the regulation of liver- and kidney-specific induction of various enzymes and proteins, respectively. Cloning deletion-breakpoint-fusion fragments caused by lethal albino deletions that genetically define the extents of themsd andhsdr-1 loci is one way of generating molecular probes for studying the gene(s) involved in these phenotypes. The distal breakpoints of five such deletions were positioned on a long-range (PFGE) map of ∼1.7 Mb of wild-type DNA surrounding thec, D7Was12, andEmv-23 loci. In addition, the distal breakpoints of two viable albino deletions, which remove part of the tyrosinase gene and extend distally, were localized in the vicinity of the lethal deletion breakpoints. Therefore, the viable deletions can be exploited to generate additional DNA probes that should facilitate the isolation of breakpoint clones from chromosomes carrying lethal deletions defininghsdr-1 andmsd.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ausubel, F.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Smith, J.A., and Struhl, K. (eds.);Current Protocols in Molecular Biology, Volume 1, John Wiley and Sons, New York, 1989.

    Google Scholar 

  • Baier, L.J., Hanash, S.M., and Erickson, R.P.: Mice homozygous for chromosomal deletions at the albino locus region lack specific polypeptides in two-dimensional gels.Proc Natl Acad Sci USA 81: 2132–2136, 1984.

    Google Scholar 

  • Bird, A.P.: CpG-rich islands and the function of DNA methylation.Nature 321: 209–213, 1986.

    Google Scholar 

  • Bird, A.P.: CpG islands as gene markers in the vertebrate nucleus.Trends Genet 3: 342–347, 1987.

    Google Scholar 

  • Brown, W.R.A. and Bird, A.P.: Long-range restriction site mapping of mammalian genomic DNA.Nature 322: 477–481, 1986.

    Google Scholar 

  • Burke, D.T., Carle, G.F., and Olson, M.V.: Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors.Science 236: 806–812, 1987.

    Google Scholar 

  • Carle, G.F. and Olsen, M.V.: An electrophoretic karyotype for yeast.Proc Natl Acad Sci USA 82: 3756–3760, 1985.

    Google Scholar 

  • Collins, F.S. and Weissman, S.M.: Directional cloning of DNA fragments at a large distance from an initial probe: A circularization method.Proc Natl Acad Sci USA 81: 6812–6816, 1984.

    Google Scholar 

  • Davisson, M.T., Roderick, T.H., and Doolittle, D.P.: Recombination percentages and chromosomal assignments.In M.F. Lyon and A.G. Searle (eds.),Genetic Variants and Strains of the Laboratory Mouse, Second Edition, pp. 432–505, Oxford University Press, New York, 1989.

    Google Scholar 

  • DeFranco, D., Morris, Jr., S.M., Leonard, C.M., and Gluecksohn-Waelsch, S.: Metallothionein mRNA expression in mice homozygous for chromosomal deletions around the albino locus.Proc Natl Acad Sci USA 85: 1161–1164, 1988.

    Google Scholar 

  • Disteche, C.M. and Adler, D.: Localization of cloned mouse chromosome 7-specific DNA to lethal albino deletions.Som Cell Mol Genet 10: 211–215, 1984.

    Google Scholar 

  • Donner, M.E., Leonard, C.M., and Gluecksohn-Waelsch, S.: Developmental regulation of constitutive and inducible expression of hepatocyte-specific genes in the mouse.Proc Natl Acad Sci USA 85: 3049–3051, 1988.

    Google Scholar 

  • Erickson, R.P., Gluecksohn-Waelsch, S., and Cori, C.F.: Glucose-6-phosphatase deficiency caused by radiation-induced alleles at the albino locus in the mouse.Proc Nat Acad Sci USA 59: 437–444, 1968.

    Google Scholar 

  • Feinberg, A.P. and Vogelstein, B.: A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Addendum.Anal Biochem 137: 267–268, 1984.

    Google Scholar 

  • Gatmaitan, Z., Lewis, S., Turchin, H., and Arias, I.M.: Premature development of ligandin (GSH transferase B) in mice with an inherited defect in endoplasmic reticulum-Golgi structure and function.Biochem Biophys Res Commun 75: 337–341, 1977.

    Google Scholar 

  • Gluecksohn-Waelsch, S.: Genetic control of morphogenetic and biochemical differentiation: Lethal albino deletions in the mouse.Cell 16: 225–237, 1979.

    Google Scholar 

  • Gluecksohn-Waelsch, S.: Regulatory genes in development.Trends Genet 3: 123–127, 1987.

    Google Scholar 

  • Gluecksohn-Waelsch, S.: Private communication.Mouse News Lett 83: 149, 1989.

    Google Scholar 

  • Goldfeld, A.E., Rubin, C.S., Siegel, T.W., Shaw, P.A., Schiffer, S.G., and Gluecksohn-Waelsch, S.: Genetic control of insulin receptors.Proc Natl Acad Sci USA 78: 6359–6361, 1981.

    Google Scholar 

  • Goldfeld, A.E., Firestone, G.L., Shaw, P.A., and Gluecksohn-Waelsch, S.: Recessive lethal deletion on mouse chromosome 7 affects glucocorticoid receptor binding activities.Proc Natl Acad Sci USA 80: 1431–1434, 1983.

    Google Scholar 

  • Green, M.C.: Catalog of mutant genes and polymorphic loci.In M.F. Lyon and A.G. Searle (eds.),Genetic Variants and Strains of the Laboratory Mouse, Second Edition, pp. 12–403, Oxford University Press, New York, 1989.

    Google Scholar 

  • Herrmann, B.G., Barlow, D.P., and Lehrach, H.: A large inverted duplication allows homologous recombination between chromosomes heterozygous for the proximalt complex inversion.Cell 48: 813–825, 1987.

    Google Scholar 

  • Herrmann, B.G., Labeit, S., Poustka, A., King, T.R., and Lehrach, H.: Cloning of theT gene required in mesoderm formation in the mouse.Nature 343: 617–622, 1990.

    Google Scholar 

  • Hillyard, A.L., Doolittle, D.P., Davisson, M.T., and Roderick, T.H.: The locus map of the mouse.Mouse Genome 89: 16–30, 1991.

    Google Scholar 

  • Johnson, D.K., Hand, Jr., R.E., and Rinchik, E.M.: Molecular mapping within the mouse albino-deletion complex.Proc Natl Acad Sci USA 86: 8862–8866, 1989.

    Google Scholar 

  • Kunkel, L.M. and co-authors: Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy.Nature 322: 73–77, 1986.

    Google Scholar 

  • Kwon, B.S., Haq, A.K., Pomerantz, S.H., and Halaban, R.: Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mousec-albino locus.Proc Natl Acad USA 84: 7473–7477, 1987.

    Google Scholar 

  • Kwon, B.S., Wakulchik, M., Haq, A.K., Halaban, R., and Kestler, D.: Sequence analysis of mouse tyrosinase cDNA and the effect of melanotropin on its gene expression.Biochem Biophys Res Common 153: 1301–1309, 1988.

    Google Scholar 

  • Lewis, S.E., Turchin, H.A., and Wojtowicz, T.E.: Fertility studies of complementing genotypes at the albino locus of the mouse.J Reprod Fertil 53: 197–202, 1978.

    Google Scholar 

  • Lindsay, S. and Bird, A.P.: Use of restriction enzymes to detect potential gene sequences in mammalian DNA.Nature 327: 336–338, 1987.

    Google Scholar 

  • Maniatis, T., Fritsch, E.F., and Sambrook, J. (eds.)Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York, 1982.

    Google Scholar 

  • McKnight, S.L., Lane, M.D., and Gluecksohn-Waelsch, S.: Is CCAAT/enhancer-binding protein a central regulator of energy metabolism?Genes Develop 3: 2021–2024, 1989.

    Google Scholar 

  • Monaco, A.P., Neve, R.L., Collati-Feener, C., Bertelson, C.J., Kurnit, D.M., and Kunkel, L.M.: Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene.Nature 323: 646–650, 1986.

    Google Scholar 

  • Morris, Jr., S.M., Moncman, C.L., Kepka, D.M., Nebes, V.L., Diven, W.F., Dizikes, G.J., Cederbaum, S.D., and DeFranco, D.: Effects of deletions in mouse chromosome 7 on expression of genes encoding the urea-cycle enzymes and phosphoenolpyruvate carboxykinase (GTP) in liver, kidney, and intestine.Biochem Genet 26: 769–781, 1988.

    Google Scholar 

  • Niswander, L., Yee, D., Rinchik, E.M., Russell, L.B., and Magnuson, T.: The albino deletion complex and early postimplantation survival in the mouse.Development 102: 45–53, 1988.

    Google Scholar 

  • Niswander, L., Yee, D., Rinchik, E.M., Russell, L.B., and Magnuson, T.: The albino-deletion complex in the mouse defines genes necessary for development of embryonic and extraembryonic ectoderm.Development 105: 175–182, 1989.

    Google Scholar 

  • Niswander, L., Kelsey, G., Schedl, A., Ruppert, S., Sharan, S.K., Holdener-Kenny, B., Rinchik, E.M., Edstrom, J-E., and Magnuson, T.: Molecular mapping of albino deletions associated with early embryonic lethality in the mouse.Genomics 9: 162–169, 1991.

    Google Scholar 

  • Petersen, D.D., Gonzalez, F.J., Rapic, V., Kozak, C.A., Lee, J.-Y., Jones, J.E., and Nebert, D.W.: Marked increases in hepatic NAD(P)H: Oxidoreductase gene transcription and mRNA levels correlated with a mouse chromosome 7 deletion.Proc Natl Acad Sci USA 86: 6699–6703, 1989.

    Google Scholar 

  • Poustka, A. and Lehrach, H.: Jumping libraries and linking libraries: The next generation of molecular tools in mammalian genetics.Trends Genet 2: 174–179, 1986.

    Google Scholar 

  • Rinchik, E.M.: Chemical mutagenesis and fine-structure functional analysis of the mouse genome.Trends Genet 7: 15–21, 1991.

    Google Scholar 

  • Rinchik, E.M., Russell, L.B., Copeland, N.G., and Jenkins, N.A.: Molecular genetic analysis of the dilute-short ear (d-se) region of the mouse.Genetics 112: 321–342, 1986.

    Google Scholar 

  • Rinchik, E.M., Machanoff, R., Cummings, C.C., and Johnson, D.K.: Molecular cloning and mapping of the ecotropic leukemia provirus Emv-23 provides molecular access to the albino-deletion complex in mouse chromosome 7.Genomics 4: 251–258, 1989.

    Google Scholar 

  • Rinchik, E.M. and Russell, L.B.: Germ-line deletion mutations in the mouse: Tools for intensive functional and physical mapping of regions of the mammalian genome.In K.E. Davies and S.M. Tilghman (eds.),Genome Analysis: Genetic and Physical Mapping, Volume 1 pp. 121–158, Cold Spring Harbor Laboratory Press, New York, 1990.

    Google Scholar 

  • Rinchik, E.M., Saunders, A.M., Holdener-Kenny, B., Sutcliffe, M.J., Brown, K.A., Brown, S.D.M., and Peters, J.: Mouse Chromosome 7.Mammalian Genome, in press, 1991.

  • Royer-Pokora, B., Kunkel, L.M., Monaco, A.P., Goff, S.C., Newburger, P.E., Baehner, R.L., Cole, F.S., Curnutte, J.T., and Orkin, S.H.: Cloning the gene for an inherited human disorderchronic granulomatous disease-on the basis of its chromosomal location.Nature 322: 32–38, 1986.

    Google Scholar 

  • Ruppert, S., Muller, G., Kwon, B., and Schutz, G.: Multiple transcripts of the mouse tyrosinase gene are generated by alternative splicing.EMBO J 7: 2715–2722, 1988.

    Google Scholar 

  • Ruppert, S., Boshart, M., Bosch, F.X., Schmid, W., Fournier, R.E.K., and Schutz, G.: Two genetically definedtrans-acting loci coordinately regulate overlapping sets of liver-specific genes.Cell 61: 895–904, 1990.

    Google Scholar 

  • Russell, L.B.: Definition of functional units in a small chromosomal segment of the mouse and its use in interpreting the nature of radiation-induced mutations.Mutat Res 11: 107–123, 1971.

    Google Scholar 

  • Russell, L.B. and DeHamer, D.L.: Complementation analysis ofc locus lethals in the mouse.Genetics 74: s236, 1973.

  • Russell, L.B., Montgomery, C.S., and Raymer, G.D.: Analysis of the albino-locus region of the mouse: IV. Characterization of 34 deficiencies.Genetics 100: 427–453, 1982.

    Google Scholar 

  • Russell, W.L.: X-ray-induced mutations in mice.Cold Spring Harbor Symp Quant Biol XVI: 327–336, 1951.

    Google Scholar 

  • Saunders, A.M. and Seldin, M.F.: A molecular genetic linkage map of mouse chromosome 7.Genomics 8: 525–535, 1990.

    Google Scholar 

  • Sodroski, J.G., Goh, W.C., and Haseltine, W.A.: Transforming potential of a human protooncogene (c-fps/fes) locus.Proc Natl Acad Sci USA 81: 3039–3043, 1984.

    Google Scholar 

  • Thaler, M.M.: Genetically determined abnormalities of microsomal enzymes in liver of mutant newborn mice.Biochem Biophys Res Commun 72: 1244–1250, 1976.

    Google Scholar 

  • Trigg, M.J. and Gluecksohn-Waelsch, S.: Ultrastructural basis of biochemical effects in a series of lethal alleles in the mouse: Neonatal and developmental studies.J Cell Biol 58: 549–563, 1973.

    Google Scholar 

  • Viskochil, D., Buchberg, A.M., Xu, G., Cawthon, R.M., Stevens, J., Wolff, R.K., Culver, M., Carey, J.C., Copeland, N.G., Jenkins, N.A., White, R., and O'Connell, P.: Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus.Cell 62: 187–192, 1990.

    Google Scholar 

  • Yokoyama, T., Silversides, D.W., Waymire, K.G., Kwon, B.S., Takevchi, T., and Overbeek, P.A.: Conserved cysteine to serine mutation in tyrosinase is responsible for the classical albino mutation in laboratory mice.Nucl Acids Res 18: 7293–7298, 1990.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klebig, M.L., Kwon, B.S. & Rinchik, E.M. Physical analysis of murine albino deletions that disrupt liver-specific gene regulation or mesoderm development. Mammalian Genome 2, 51–63 (1991). https://doi.org/10.1007/BF00570440

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00570440

Keywords

Navigation