INTERLEUKIN-2 PROMOTER ENHANCER CONTROLLED EXPRESSION OF A SYNTHETIC CECROPIN-CLASS LYTIC PEPTIDE IN TRANSGENIC MICE AND SUBSEQUENT RESISTANCE TO BRUCELLA-ABORTUS/

The addition of an antimicrobial that can be synthesized by the mammal ian immune system at the point of challenge may enhance disease resist ance. A possible group of agents are cecropins, broad-spectrum antimic robial 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, Shiv a la (a synthetic cecropinclass lytic peptide), and the SV40 polyadeny lation/splice signal. A reverse-transcription PCR assay determined tha t two lines of transgenic mice were produced whose spleen-derived lymp hocytes could be induced to transcribe and mature mRNA for Shiva la by exposure to 3.25 mg ml(-1) of Con A. Two lines were challenged with a n inoculation of 5 X 10(4) Brucella abortus strain 2308. After four we eks, there were significantly fewer B. abortus organisms in the spleen s of transgenic mice than in non-transgenic control mice of the same s train (p < 0.05). Since the controlling regions of the IL-2 enhancer a nd the amino acid sequence of the signal peptide are highly conserved among several species, it is likely that this recombinant gene will fu nction in other mammals.