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Proc Natl Acad Sci U S A. Jun 6, 1995; 92(12): 5371–5375.
PMCID: PMC41696

Position-dependent variegation of globin transgene expression in mice.

Abstract

Expression of genes in eukaryotes has commonly been analyzed in a whole tissue, and levels of expression have been interpreted as the result of equivalent rates of transcription in every cell. We have produced transgenic mouse lines that express beta-galactosidase under the control of globin promoters linked to the major tissue-specific regulatory element of the alpha-globin locus, which permits the analysis of transgene expression in individual red blood cells. We find that expression of the transgene within all mouse lines is heterocellular. Individual cells either do not express the transgene at all or express it at a level characteristic of that line. The number of beta-galactosidase-expressing cells varies greatly between different lines of transgenic mice at any defined stage of development, but within a transgenic line, individual mice have strikingly similar numbers of expressing cells. This suggests that the degree of heterocellular expression is determined by the site of integration, as is seen in position-effect variegation.

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  • Mintz B, Bradl M. Mosaic expression of a tyrosinase fusion gene in albino mice yields a heritable striped coat color pattern in transgenic homozygotes. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9643–9647. [PMC free article] [PubMed]
  • Bradl M, Larue L, Mintz B. Clonal coat color variation due to a transforming gene expressed in melanocytes of transgenic mice. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6447–6451. [PMC free article] [PubMed]
  • Rubin DC, Ong DE, Gordon JI. Cellular differentiation in the emerging fetal rat small intestinal epithelium: mosaic patterns of gene expression. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1278–1282. [PMC free article] [PubMed]
  • Sweetser DA, Hauft SM, Hoppe PC, Birkenmeier EH, Gordon JI. Transgenic mice containing intestinal fatty acid-binding protein-human growth hormone fusion genes exhibit correct regional and cell-specific expression of the reporter gene in their small intestine. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9611–9615. [PMC free article] [PubMed]
  • Wu H, Fässler R, Schnieke A, Barker D, Lee KH, Chapman V, Francke U, Jaenisch R. An X-linked human collagen transgene escapes X inactivation in a subset of cells. Development. 1992 Nov;116(3):687–695. [PubMed]
  • McGowan R, Campbell R, Peterson A, Sapienza C. Cellular mosaicism in the methylation and expression of hemizygous loci in the mouse. Genes Dev. 1989 Nov;3(11):1669–1676. [PubMed]
  • Pravtcheva DD, Wise TL, Ensor NJ, Ruddle FH. Mosaic expression of an Hprt transgene integrated in a region of Y heterochromatin. J Exp Zool. 1994 May 1;268(6):452–468. [PubMed]
  • Allshire RC, Javerzat JP, Redhead NJ, Cranston G. Position effect variegation at fission yeast centromeres. Cell. 1994 Jan 14;76(1):157–169. [PubMed]
  • Grosveld F, van Assendelft GB, Greaves DR, Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. [PubMed]
  • Fraser P, Hurst J, Collis P, Grosveld F. DNaseI hypersensitive sites 1, 2 and 3 of the human beta-globin dominant control region direct position-independent expression. Nucleic Acids Res. 1990 Jun 25;18(12):3503–3508. [PMC free article] [PubMed]
  • Jarman AP, Wood WG, Sharpe JA, Gourdon G, Ayyub H, Higgs DR. Characterization of the major regulatory element upstream of the human alpha-globin gene cluster. Mol Cell Biol. 1991 Sep;11(9):4679–4689. [PMC free article] [PubMed]
  • Higgs DR, Wood WG, Jarman AP, Sharpe J, Lida J, Pretorius IM, Ayyub H. A major positive regulatory region located far upstream of the human alpha-globin gene locus. Genes Dev. 1990 Sep;4(9):1588–1601. [PubMed]
  • Sharpe JA, Chan-Thomas PS, Lida J, Ayyub H, Wood WG, Higgs DR. Analysis of the human alpha globin upstream regulatory element (HS-40) in transgenic mice. EMBO J. 1992 Dec;11(12):4565–4572. [PMC free article] [PubMed]
  • Sharpe JA, Wells DJ, Whitelaw E, Vyas P, Higgs DR, Wood WG. Analysis of the human alpha-globin gene cluster in transgenic mice. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11262–11266. [PMC free article] [PubMed]
  • Gourdon G, Sharpe JA, Wells D, Wood WG, Higgs DR. Analysis of a 70 kb segment of DNA containing the human zeta and alpha-globin genes linked to their regulatory element (HS-40) in transgenic mice. Nucleic Acids Res. 1994 Oct 11;22(20):4139–4147. [PMC free article] [PubMed]
  • Pondel MD, Proudfoot NJ, Whitelaw C, Whitelaw E. The developmental regulation of the human zeta-globin gene in transgenic mice employing beta-galactosidase as a reporter gene. Nucleic Acids Res. 1992 Nov 11;20(21):5655–5660. [PMC free article] [PubMed]
  • Herbomel P, Bourachot B, Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. [PubMed]
  • Stamatoyannopoulos G, Josephson B, Zhang JW, Li Q. Developmental regulation of human gamma-globin genes in transgenic mice. Mol Cell Biol. 1993 Dec;13(12):7636–7644. [PMC free article] [PubMed]
  • Enver T, Li Q, Gale KB, Hu M, May GE, Karlinsey JE, Jimenez G, Papayannopoulou T, Costantini F. Analysis of the developmental and transcriptional potentiation functions of 5'HS2 of the murine beta-globin locus control region in transgenic mice. Dev Biol. 1994 Oct;165(2):574–584. [PubMed]
  • TILL JE, MCCULLOCH EA, SIMINOVITCH L. A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS. Proc Natl Acad Sci U S A. 1964 Jan;51:29–36. [PMC free article] [PubMed]
  • Orkin SH, Harosi FI, Leder P. Differentiation in erythroleukemic cells and their somatic hybrids. Proc Natl Acad Sci U S A. 1975 Jan;72(1):98–102. [PMC free article] [PubMed]
  • Gusella J, Geller R, Clarke B, Weeks V, Housman D. Commitment to erythroid differentiation by friend erythroleukemia cells: a stochastic analysis. Cell. 1976 Oct;9(2):221–229. [PubMed]
  • Buratowski S. The basics of basal transcription by RNA polymerase II. Cell. 1994 Apr 8;77(1):1–3. [PubMed]
  • Cattanach BM. Position effect variegation in the mouse. Genet Res. 1974 Jun;23(3):291–306. [PubMed]

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