Volume 6, Number 5, 337-347, DOI: 10.1023/A:1018423015014

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

WILLIAM A. Reed, PHILIP H. Elzer, FRED M. Enright, JESSE M. Jaynes, JOHN D. Morrey and KENNETH L. White

View Related Documents

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 5prime-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="">

brucellosis - cecropin - gene therapy - interleukin 2 - Shiva 1

Fulltext Preview

Image of the first page of the fulltext document