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Interleukin 2 promoter/enhancer controlled expression of a synthetic cecropin-class lytic peptide in transgenic mice and subsequent resistance to Brucella abortus

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Abstract

The addition of an antimicrobial that can be synthesized by the mammalian immune system at the point of challenge may enhance disease resistance. A possible group of agents are cecropins, broad-spectrum antimicrobial peptides, which have been described and characterized. They are relatively non-toxic to normal cells from multicellular organisms but are toxic to a wide range of bacteria, protozoa and fungi, as well as infected and abnormal cells. Twenty-six lines of transgenic mice were produced by pronuclear injection of DNA consisting of the 5′-flanking region from −593 to +110 of the mouse interleukin 2 (IL-2) gene, Shiva 1a (a synthetic cecropin-class lytic peptide), and the SV40 polyadenylation/splice signal. A reverse-transcription PCR assay determined that two lines of transgenic mice were produced whose spleen-derived lymphocytes could be induced to transcribe and mature mRNA for Shiva 1a by exposure to 3.25 mg ml−1 of Con A. Two lines were challenged with an inoculation of 5 × 104 Brucella abortus strain 2308. After four weeks, there were significantly fewer B. abortus organisms in the spleens of transgenic mice than in non-transgenic control mice of the same strain (p < 0.05). Since the controlling regions of the IL-2 enhancer and the amino acid sequence of the signal peptide are highly conserved among several species, it is likely that this recombinant gene will function in other mammals

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Authors and Affiliations

  1. Department of Animal, Dairy, and Veterinary Sciences, Logan, Utah State University Utah, USA

    WILLIAM A. Reed & JOHN D. Morrey

  2. Department of Veterinary Science, Louisiana State University, Baton Rouge, USA

    PHILIP H. Elzer & FRED M. Enright

  3. 201 Biotechnology Centre, Logan, Utah State University, Utah, USA

    JESSE M. Jaynes

  4. Department of Biochemistry, Baton Rouge, USA

    KENNETH L. White

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  1. WILLIAM A. Reed
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  2. PHILIP H. Elzer
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  3. FRED M. Enright
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  4. JESSE M. Jaynes
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  5. JOHN D. Morrey
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  6. KENNETH L. White
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Reed, W.A., Elzer, P.H., Enright, F.M. et al. Interleukin 2 promoter/enhancer controlled expression of a synthetic cecropin-class lytic peptide in transgenic mice and subsequent resistance to Brucella abortus. Transgenic Res 6, 337–347 (1997). https://doi.org/10.1023/A:1018423015014

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