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Title: ANALYSIS OF PHYSIOLOGICAL ROLE OF LACTOFERRIN USING KNOCKOUT AND TRANSGENIC MOUSE MODELS

Author
item WARD, P - BAYLOR COLL OF MEDICINE
item MENDOZA-MENESES, M - BAYLOR COLL OF MEDICINE
item PARK, P - BAYLOR COLL OF MEDICINE
item DEMAYO, F - BAYLOR COLL OF MEDICINE
item CONNEELY, O - BAYLOR COLL OF MEDICINE

Submitted to: Nutrition Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 10/1/2002
Publication Date: 1/2/2003
Citation: Ward, P.P., Mendoza-Meneses, M., Park, P.W., Demayo, F.J., Conneely, O.M. 2003. Analysis of physiological role of lactoferrin using knockout and transgenic mouse models. 6th International Conference on Lactoferrin: Structure, Function and Applications, Capri, Italy. p. 95.

Interpretive Summary: Interpretive Summary not needed for this 115.

Technical Abstract: Lactoferrin (LF) is an iron-binding glycoprotein present in milk, mucosal secretions and in the secondary granules of neutrophils. While several functions have been proposed for lactoferrin, including regulation of iron homeostasis and host response to infection and inflammation, the exact physiological role of LF in vivo remains to be established. To directly address the essential physiological functions of lactoferrin, we have generated lactoferrin knock-out mice (LFKO-/-) by homologous gene targeting. LFKO-/- mice are viable and fertile, develop normally and display no gross abnormalities. Iron status and host response to infection (Pseudomonas aeruginosa) and inflammatory challenge (Lipopolysaccharide and Thioglycollate) were normal in LFKO-/- mice demonstrating that LF does not play a major non-redundant role in these functions. In a second approach, we have generated transgenic mice that target overexpression of lactoferrin to the intestine or lung using a liver fatty acid binding promoter and surfactant protein C promoter, respectively. Studies are currently underway to determine the consequences of lactoferrin overexpression on iron status and resistance to bacterial and inflammatory challenges. These studies should provide new insights on the role of LF in iron homeostasis and host defense at the mucosal surface, in addition to providing data on the potential benefits of LF supplementation in the prevention of microbial and inflammatory disease.