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Title: GROWTH AND TISSUE ACCRETION RATES OF SWINE EXPESSSING AN INSULIN-LIKE FACTOR I TRANSGENE.

Author
item KERR, DAVID - UNIVERSITY OF VERMONT
item PLAUT, KAREN - UNIVERSITY OF VERMONT
item BRAMLEY, JOHN - UNIVERSITY OF VERMONT
item WILLIAMSON, CHRISTINE - COMPTON LABORATORY
item LAX, ALISTAIR - COMPTON LABORATORY
item Wells, Kevin
item MOORE, KAREN - 1265-45-00
item Wall, Robert

Submitted to: Animal Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/24/2003
Publication Date: N/A
Citation: N/A

Interpretive Summary: Mastitis is the most economically important disease in dairy cattle. In addition having an adverse affect on the well being of about a third of the US dairy cow population it cost our dairy industry approximately $2 billion annually. Improved management practices and prophylactic antibiotic treatment have failed to control the disease. We believe a genetic engineering approach may be the most effective way to rid the industry of this pervasive problem. To test that hypothesis we created a gene that was designed to produce lysostaphin specifically in mammary glands and used the gene to produce transgenic mice. Lysostaphin is a protein that is very affective at killing Staphylococcus aureus, the major contagious mastitis pathogen. As expected the transgenic mice produced lysostaphin in their milk. When milk from those animals was mixed with S. aureus, the bacteria died. Furthermore, when S. aureus was infused into the mammary glands of the transgenic mice the mice making the most lysostaphin were completely protected. Mice making lower amounts of lysostaphin were partially protected. When the same infusion was performed on non-transgenic control mice their mammary glands were destroyed by the infection within 24 hours. We believe this novel approach will have the same benificial protective affect in dairy cattle.

Technical Abstract: Infection of the mammary gland, in addition to causing animal distress, is a major economic burden of the dairy industry. Staphylococcus aureus is the major contagious mastitis pathogen, accounting for approximately 15% to 30% of infections, and has proven difficult to control using standard management practices. As a first step towards enhancing mastitis resistance of dairy animals we report the generation of transgenic mice that secrete a potent antistaphylococcal protein into milk. The protein-lysostaphin-is a peptidoglycan hydrolase normally produced by S. simulans. When secreted by eukaryotic cells it becomes glycosylated and inactive. Removal of two glycosylation motifs through engineering asparagine to glutamine codon substitutions enables secretion of a bioactive variant. Three lines of transgenic mice have now been examined in which the 5'-flanking region of ovine b-lactoglobulin gene directed the secretion of up to Gln125, 232- lysostaphin into milk at concentrations of approximately 75 mg/ml, 150 mg/ml, and 1 mg/ml. These mice exhibit substantial resistance to an intramammary challenge of 104 colony forming units of Staphylococcus aureus, with the highest expressing line being completely resistant. Milk protein profiles of transgenic and non-transgenic mice are similar. These results clearly demonstrate the potential of genetic engineering to combat the most prevalent disease of dairy cattle.