title: Interleukin 2 promoter/enhancer controlled expression of a synthetic cecropin-class lytic peptide in transgenic mice and subsequent resistance to Brucella abortus.
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 cecropinclass 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 x 10(4) 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.
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Logan, Utah State University 84322-4700, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Reed
authors.forename: P H
authors.initials: PH
authors.lastname: Elzer
authors.forename: F M
authors.initials: FM
authors.lastname: Enright
authors.forename: J M
authors.initials: JM
authors.lastname: Jaynes
authors.forename: J D
authors.initials: JD
authors.lastname: Morrey
authors.forename: K L
authors.initials: KL
authors.lastname: White
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D002003:Brucella abortus; D002006:Brucellosis / Q000276:immunology / Q000517:prevention & control; D004742:Enhancer Elements, Genetic; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic / Q000235:genetics*; D010455:Peptides / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000382:microbiology; D019076:Transgenes
chemical_list: D023181:Antimicrobial Cationic Peptides; D007376:Interleukin-2; D010455:Peptides; D011993:Recombinant Fusion Proteins; C057355:Shiva-1