• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of narLink to Publisher's site
Nucleic Acids Res. Nov 25, 1991; 19(22): 6205–6208.
PMCID: PMC329125

The variability in activity of the universally expressed human cytomegalovirus immediate early gene 1 enhancer/promoter in transgenic mice.

Abstract

Transcriptional control regions which direct transgene expression to all tissues in transgenic animals can be useful tools for gain-of-function experiments in transgenic animals. A candidate for this purpose is the regulatory region of the human cytomegalovirus immediate early 1 gene (HCMVIE1) which is highly expressed in many lines of tissue culture cells. Here we analyzed the activity of the HCMVIE1 enhancer/promoter using a sensitive reporter gene, the bacterial chloramphenicol acetyltransferase (CAT) gene. Three lines of transgenic mice with an intact transgene were established. All 3 lines expressed the transgene in all 28 tissues analyzed; however, levels of expression between the three lines varied up to 100,000 fold. In addition, expression levels in the high expressing line varied over a 10,000 fold continuum, while expression levels between tissues was almost uniform in the lowest expressing line. The transgene was well expressed in the high expressing line; CAT activity in the highest expressing tissues was equivalent to levels previously reported for tissue specific CAT transgenes active only in a limited number of tissues. These data support the utilization of the HCMVIE1 enhancer/promoter as a means of expressing a transgene in all tissues, but indicate that lines with substantially different overall levels of expression may be generated, and that markedly different levels of tissue specific expression may be found when the overall level of transgene expression is high.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (750K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Boshart M, Weber F, Jahn G, Dorsch-Häsler K, Fleckenstein B, Schaffner W. A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell. 1985 Jun;41(2):521–530. [PubMed]
  • Chang YN, Crawford S, Stall J, Rawlins DR, Jeang KT, Hayward GS. The palindromic series I repeats in the simian cytomegalovirus major immediate-early promoter behave as both strong basal enhancers and cyclic AMP response elements. J Virol. 1990 Jan;64(1):264–277. [PMC free article] [PubMed]
  • Fang XJ, Keating A, de Villiers J, Sherman M. Tissue-specific activity of heterologous viral promoters in primary rat hepatocytes and Hep G2 cells. Hepatology. 1989 Nov;10(5):781–787. [PubMed]
  • Fickenscher H, Stamminger T, Rüger R, Fleckenstein B. The role of a repetitive palindromic sequence element in the human cytomegalovirus major immediate early enhancer. J Gen Virol. 1989 Jan;70(Pt 1):107–123. [PubMed]
  • Foecking MK, Hofstetter H. Powerful and versatile enhancer-promoter unit for mammalian expression vectors. Gene. 1986;45(1):101–105. [PubMed]
  • Ghazal P, Lubon H, Fleckenstein B, Hennighausen L. Binding of transcription factors and creation of a large nucleoprotein complex on the human cytomegalovirus enhancer. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3658–3662. [PMC free article] [PubMed]
  • Ghazal P, Lubon H, Hennighausen L. Multiple sequence-specific transcription factors modulate cytomegalovirus enhancer activity in vitro. Mol Cell Biol. 1988 Apr;8(4):1809–1811. [PMC free article] [PubMed]
  • Hunninghake GW, Monick MM, Liu B, Stinski MF. The promoter-regulatory region of the major immediate-early gene of human cytomegalovirus responds to T-lymphocyte stimulation and contains functional cyclic AMP-response elements. J Virol. 1989 Jul;63(7):3026–3033. [PMC free article] [PubMed]
  • Keating A, Horsfall W, Hawley RG, Toneguzzo F. Effect of different promoters on expression of genes introduced into hematopoietic and marrow stromal cells by electroporation. Exp Hematol. 1990 Feb;18(2):99–102. [PubMed]
  • Krippl B, Griep AE, Mahon KA, Böhnlein E, Gruss P, Westphal H. Expression and amplification in transgenic mice of a polyoma virus mutant regulatory region. Nucleic Acids Res. 1988 Sep 26;16(18):8963–8976. [PMC free article] [PubMed]
  • Leonard J, Khillan JS, Gendelman HE, Adachi A, Lorenzo S, Westphal H, Martin MA, Meltzer MS. The human immunodeficiency virus long terminal repeat is preferentially expressed in Langerhans cells in transgenic mice. AIDS Res Hum Retroviruses. 1989 Aug;5(4):421–430. [PubMed]
  • Low MJ, Goodman RH, Ebert KM. Cryptic human growth hormone gene sequences direct gonadotroph-specific expression in transgenic mice. Mol Endocrinol. 1989 Dec;3(12):2028–2033. [PubMed]
  • Merlie JP, Kornhauser JM. Neural regulation of gene expression by an acetylcholine receptor promoter in muscle of transgenic mice. Neuron. 1989 Apr;2(4):1295–1300. [PubMed]
  • Muller SR, Sullivan PD, Clegg DO, Feinstein SC. Efficient transfection and expression of heterologous genes in PC12 cells. DNA Cell Biol. 1990 Apr;9(3):221–229. [PubMed]
  • Niller HH, Hennighausen L. Phytohemagglutinin-induced activity of cyclic AMP (cAMP) response elements from cytomegalovirus is reduced by cyclosporine and synergistically enhanced by cAMP. J Virol. 1990 May;64(5):2388–2391. [PMC free article] [PubMed]
  • Niller HH, Hennighausen L. Formation of several specific nucleoprotein complexes on the human cytomegalovirus immediate early enhancer. Nucleic Acids Res. 1991 Jul 11;19(13):3715–3721. [PMC free article] [PubMed]
  • Overbeek PA, Lai SP, Van Quill KR, Westphal H. Tissue-specific expression in transgenic mice of a fused gene containing RSV terminal sequences. Science. 1986 Mar 28;231(4745):1574–1577. [PubMed]
  • Palmiter RD, Brinster RL. Germ-line transformation of mice. Annu Rev Genet. 1986;20:465–499. [PubMed]
  • Reik W, Williams G, Barton S, Norris M, Neuberger M, Surani MA. Provision of the immunoglobulin heavy chain enhancer downstream of a test gene is sufficient to confer lymphoid-specific expression in transgenic mice. Eur J Immunol. 1987 Apr;17(4):465–469. [PubMed]
  • Rosenthal N, Kornhauser JM, Donoghue M, Rosen KM, Merlie JP. Myosin light chain enhancer activates muscle-specific, developmentally regulated gene expression in transgenic mice. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7780–7784. [PMC free article] [PubMed]
  • Schmidt EV, Christoph G, Zeller R, Leder P. The cytomegalovirus enhancer: a pan-active control element in transgenic mice. Mol Cell Biol. 1990 Aug;10(8):4406–4411. [PMC free article] [PubMed]
  • Stamminger T, Fickenscher H, Fleckenstein B. Cell type-specific induction of the major immediate early enhancer of human cytomegalovirus by cyclic AMP. J Gen Virol. 1990 Jan;71(Pt 1):105–113. [PubMed]
  • Stinski MF, Roehr TJ. Activation of the major immediate early gene of human cytomegalovirus by cis-acting elements in the promoter-regulatory sequence and by virus-specific trans-acting components. J Virol. 1985 Aug;55(2):431–441. [PMC free article] [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...