Transgenic Cows That Produce Recombinant Human Lactoferrin in Milk Are Not Protected from Experimental Escherichia coli Intramammary Infection

This is the first study describing an experimental mastitis model using transgenic cows expressing recombinant human lactoferrin (rhLf) in their milk. The aim of the study was to investigate the concentrations in milk and protective effects of bovine and recombinant human lactoferrin in experimental...

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Bibliographic Details
Published in:	Infection and Immunity Vol. 74; no. 11; pp. 6206 - 6212
Main Authors:	Hyvönen, P, Suojala, L, Orro, T, Haaranen, J, Simola, O, Røntved, C, Pyörälä, S
Format:	Journal Article
Language:	English
Published:	Washington, DC American Society for Microbiology 01-11-2006
Subjects:	Animals Animals, Genetically Modified Bacterial Infections Biological and medical sciences Carrier Proteins - biosynthesis Carrier Proteins - genetics Carrier Proteins - physiology Cattle - genetics Cattle - microbiology Escherichia coli Escherichia coli Infections - microbiology Female Fundamental and applied biological sciences. Psychology Humans Lactoferrin Mastitis, Bovine - microbiology Microbiology Recombinant Proteins - biosynthesis Recombinant Proteins - genetics Human Bovine Microbiology Colibacillosis Immunity Infection Vertebrata Lactoferrin Mammalia Bacteriosis Artiodactyla Veterinary Ungulata Milk
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Summary:	This is the first study describing an experimental mastitis model using transgenic cows expressing recombinant human lactoferrin (rhLf) in their milk. The aim of the study was to investigate the concentrations in milk and protective effects of bovine and recombinant human lactoferrin in experimental Escherichia coli mastitis. Experimental intramammary infection was induced in one udder quarter of seven first-lactating rhLf-transgenic cows and six normal cows, using an E. coli strain isolated from cows with clinical mastitis and known to be susceptible to Lf in vitro. Clinical signs were recorded during the experimental period, concentrations of human and bovine Lf and indicators of inflammation and bacterial counts were determined for milk, and concentrations of acute-phase proteins and tumor necrosis factor alpha were determined for sera and milk. Serum cortisol and blood hematological and biochemical parameters were also determined. Expression levels of rhLf in the milk of transgenic cows remained constant throughout the experiment (mean, 2.9 mg/ml). The high Lf concentrations in the milk of transgenic cows did not protect them from intramammary infection. All cows became infected and developed clinical mastitis. The rhLf-transgenic cows showed milder systemic signs and lower serum cortisol and haptoglobin concentrations than did controls. This may be explained by lipopolysaccharide-neutralizing and immunomodulatory effects of the high Lf concentrations in their milk. However, Lf does not seem to be a very efficient protein for genetic engineering to enhance the mastitis resistance of dairy cows.
Bibliography:	http://iai.asm.org/ ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Corresponding author. Mailing address: Institute of Applied Biotechnology, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio, Finland. Phone: 358 17 163564. Fax: 358 17 163322. E-mail: paula.hyvonen@uku.fi. Editor: J. L. Flynn
ISSN:	0019-9567 1098-5522
DOI:	10.1128/IAI.00238-06