Genetic engineering of livestock to improve human health: The human lysozyme transgenic goat model
Maga, Elizabeth AMurray, James D
Background: Transgenic animals have been generated for a variety of purposes including research tools, medical models, bioreactors (dairy animals producing human pharmaceuticals in their milk or in the egg whites of chickens) and for production agriculture (animals with increased growth, decreased environmental pollution, disease resistance), which includes the generation of animals designed to benefit human health. For example, transgenic goats expressing human lysozyme in their milk are being used as a model method to supply milk with antibacterial properties to help fight diarrheal illnesses in children. Lysozyme is a naturally occurring antimicrobial found in human milk at much higher levels than in the milk of dairy goats and cows. Lysozyme serves as part of the natural defense system against infection and also helps establish a healthy gut microbiota in the infant. We hypothesized that the presence of increased levels of lysozyme in the milk of dairy goats could offer several benefits that affect human health, including the promotion of a healthy gut microbiota and associated benefits such as improved growth and resistance to intestinal infections. Review: Research with this line of transgenic goats over the last 12 years has demonstrated that the presence and expression of the human lysozyme transgene is not detrimental to the animals themselves and that the milk can indeed act in an antimicrobial fashion when consumed by pigs, a model animal for human health, and impact the state of the intestine in a positive manner. Pigs consuming milk from human lysozyme transgenic goats had significantly lower levels of coliforms and E. coli in their intestine than did pigs consuming milk from non-transgenic control animals. In addition to bacterial changes, intestinal tissue of pigs consuming milk from lysozyme transgenic goats had a significantly larger surface area with significantly fewer intraepithelial lymphocytes and an elevated level of expression of the anti-inflammatory cytokine TGF-â1 compared to control-fed animals, all indicators of a healthier intestinal tract. Metabolite profile analysis demonstrated significant differences in the levels of 18 metabolites in the serum of pigs fed lysozyme milk with the direction of changes beneficial to the health of the animal. Finally, pigs consuming milk from lysozyme transgenic goats were more resistant to infection when challenged with an enteropathogenic E. coli, indicating a protective effect of lysozyme milk. In the semi-arid northeast of Brazil, 89 of 1000 children die before they reach the age of 2 years and 17% of these deaths can be attributed to diarrhea. The use of genetically engineered animals containing increased levels of lysozyme in their milk is a novel and simple approach to fight this problem. Work will be presented outlining the characterization of these animals and the impact of consuming the milk with the goal of one day having the milk available as a preventative or treatment agent for diarrheal illnesses. Conclusions: Genetic engineering is a viable approach to produce animal food products that can be used to improve human health. Brazil's acceptance of this technology has positioned itself at the forefront to demonstrate to the world a new tool to help fight common diarrhea and its impact on the growth and development of children.
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