Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1997 Mar 1;25(5):1009–1014. doi: 10.1093/nar/25.5.1009

Mammalian cDNA and prokaryotic reporter sequences silence adjacent transgenes in transgenic mice.

A J Clark 1, G Harold 1, F E Yull 1
PMCID: PMC146529  PMID: 9023112

Abstract

The ovine beta-lactoglobulin gene is expressed efficiently and at high levels in the mammary gland of transgenic mice. In contrast, when this gene is linked to a second gene construct comprising a mammalian cDNA or a CAT reporter sequence it fails to be expressed in the majority of transgenic lines generated. We suggest that mammalian cDNAs and prokaryotic reporter sequences can serve as active foci for gene silencing in the mammalian genome.

Full Text

The Full Text of this article is available as a PDF (111.8 KB).

Selected References

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

  1. Allshire R. C., Javerzat J. P., Redhead N. J., Cranston G. Position effect variegation at fission yeast centromeres. Cell. 1994 Jan 14;76(1):157–169. doi: 10.1016/0092-8674(94)90180-5. [DOI] [PubMed] [Google Scholar]
  2. Brinster R. L., Allen J. M., Behringer R. R., Gelinas R. E., Palmiter R. D. Introns increase transcriptional efficiency in transgenic mice. Proc Natl Acad Sci U S A. 1988 Feb;85(3):836–840. doi: 10.1073/pnas.85.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burdon T. G., Maitland K. A., Clark A. J., Wallace R., Watson C. J. Regulation of the sheep beta-lactoglobulin gene by lactogenic hormones is mediated by a transcription factor that binds an interferon-gamma activation site-related element. Mol Endocrinol. 1994 Nov;8(11):1528–1536. doi: 10.1210/mend.8.11.7877621. [DOI] [PubMed] [Google Scholar]
  4. Clark A. J., Cowper A., Wallace R., Wright G., Simons J. P. Rescuing transgene expression by co-integration. Biotechnology (N Y) 1992 Nov;10(11):1450–1454. doi: 10.1038/nbt1192-1450. [DOI] [PubMed] [Google Scholar]
  5. Dobie K. W., Lee M., Fantes J. A., Graham E., Clark A. J., Springbett A., Lathe R., McClenaghan M. Variegated transgene expression in mouse mammary gland is determined by the transgene integration locus. Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6659–6664. doi: 10.1073/pnas.93.13.6659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dorer D. R., Henikoff S. Expansions of transgene repeats cause heterochromatin formation and gene silencing in Drosophila. Cell. 1994 Jul 1;77(7):993–1002. doi: 10.1016/0092-8674(94)90439-1. [DOI] [PubMed] [Google Scholar]
  7. Felsenfeld G. Chromatin unfolds. Cell. 1996 Jul 12;86(1):13–19. doi: 10.1016/s0092-8674(00)80073-2. [DOI] [PubMed] [Google Scholar]
  8. Guy L. G., Kothary R., DeRepentigny Y., Delvoye N., Ellis J., Wall L. The beta-globin locus control region enhances transcription of but does not confer position-independent expression onto the lacZ gene in transgenic mice. EMBO J. 1996 Jul 15;15(14):3713–3721. [PMC free article] [PubMed] [Google Scholar]
  9. Karpen G. H. Position-effect variegation and the new biology of heterochromatin. Curr Opin Genet Dev. 1994 Apr;4(2):281–291. doi: 10.1016/s0959-437x(05)80055-3. [DOI] [PubMed] [Google Scholar]
  10. Liu K., Sandgren E. P., Palmiter R. D., Stein A. Rat growth hormone gene introns stimulate nucleosome alignment in vitro and in transgenic mice. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7724–7728. doi: 10.1073/pnas.92.17.7724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McKnight R. A., Wall R. J., Hennighausen L. Expression of genomic and cDNA transgenes after co-integration in transgenic mice. Transgenic Res. 1995 Jan;4(1):39–43. doi: 10.1007/BF01976500. [DOI] [PubMed] [Google Scholar]
  12. Palmiter R. D., Brinster R. L. Germ-line transformation of mice. Annu Rev Genet. 1986;20:465–499. doi: 10.1146/annurev.ge.20.120186.002341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Palmiter R. D., Sandgren E. P., Avarbock M. R., Allen D. D., Brinster R. L. Heterologous introns can enhance expression of transgenes in mice. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):478–482. doi: 10.1073/pnas.88.2.478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pardy K. Reporter enzymes for the study of promoter activity. Mol Biotechnol. 1994 Aug;2(1):23–27. doi: 10.1007/BF02789287. [DOI] [PubMed] [Google Scholar]
  15. Simons J. P., McClenaghan M., Clark A. J. Alteration of the quality of milk by expression of sheep beta-lactoglobulin in transgenic mice. Nature. 1987 Aug 6;328(6130):530–532. doi: 10.1038/328530a0. [DOI] [PubMed] [Google Scholar]
  16. Tartof K. D., Bremer M. Mechanisms for the construction and developmental control of heterochromatin formation and imprinted chromosome domains. Dev Suppl. 1990:35–45. [PubMed] [Google Scholar]
  17. Townes T. M., Lingrel J. B., Chen H. Y., Brinster R. L., Palmiter R. D. Erythroid-specific expression of human beta-globin genes in transgenic mice. EMBO J. 1985 Jul;4(7):1715–1723. doi: 10.1002/j.1460-2075.1985.tb03841.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Webster J., Wallace R. M., Clark A. J., Whitelaw C. B. Tissue-specific, temporally regulated expression mediated by the proximal ovine beta-lactoglobulin promoter in transgenic mice. Cell Mol Biol Res. 1995;41(1):11–15. [PubMed] [Google Scholar]
  19. Whitelaw C. B., Archibald A. L., Harris S., McClenaghan M., Simons J. P., Clark A. J. Targeting expression to the mammary gland: intronic sequences can enhance the efficiency of gene expression in transgenic mice. Transgenic Res. 1991 Dec;1(1):3–13. doi: 10.1007/BF02512991. [DOI] [PubMed] [Google Scholar]
  20. Whitelaw C. B., Harris S., McClenaghan M., Simons J. P., Clark A. J. Position-independent expression of the ovine beta-lactoglobulin gene in transgenic mice. Biochem J. 1992 Aug 15;286(Pt 1):31–39. doi: 10.1042/bj2860031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yull F., Harold G., Wallace R., Cowper A., Percy J., Cottingham I., Clark A. J. Fixing human factor IX (fIX): correction of a cryptic RNA splice enables the production of biologically active fIX in the mammary gland of transgenic mice. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10899–10903. doi: 10.1073/pnas.92.24.10899. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES