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Genetically Engineered Cow Produces Hypoallergenic Milk

Melissa Lee Phillips

What technique did a team from New Zealand use to genetically engineer a cow to produce hypoallergenic milk? And what protein did they target?

New Zealand researchers have engineered a cow that produces hypoallergenic milk, according to a paper in this week's Proceedings of the National Academy of Sciences (1). They used RNA interference (RNAi), in which small RNA molecules prevent protein expression, to knock down production of an allergenic milk protein.

Daisy the cow produces milk free of ß-lactoglobulin and high in casein. Credit: AgResearch

Milk from dairy cows contains a whey protein called β-lactoglobulin (BLG) that isn't found in human milk. It's estimated that 2-3% of babies are allergic to cow milk and BLG is thought to be a major cause of these allergies, which can cause diarrhea and vomiting.

Baby formula based on cow's milk is hydrolyzed to break down whey proteins, but the remaining peptides can still cause allergic reactions. To remove BLG completely from milk, researchers have been interested in developing transgenic cows, said study author Stefan Wagner, a scientist at AgResearch in Hamilton, New Zealand.

Attempts to knock-out gene expression in livestock animals have been largely unsuccessful, so Wagner and his colleagues tried another approach, RNAi. They artificially created microRNA molecules that interfere with BLG expression. They first tested these molecules in vitro to find the version best able to block BLG production.

After selecting one BLG microRNA and testing its efficacy in genetically engineered mice, the researchers inserted DNA encoding it into the cattle genome and used nuclear transfer to create genetically modified cow embryos. Out of about 100 embryos, they achieved five pregnancies, only one of which led to the birth of a calf, named Daisy.

When Daisy was seven-months-old, the researchers induced lactation and found that her milk contained no detectable BLG. They also found that all the other major milk proteins, especially the caseins, are present at abnormally high levels in Daisy's milk—which the authors suggest should mean higher-calcium milk and potentially increased cheese yields.

But getting such milk approved for consumers will be a lengthy process. Currently, the researchers are attempting to demonstrate that the milk is in fact less allergenic to mice. "We're not yet testing this for clinical trials," said Wagner.

Meanwhile, they hope to use a BLG-free line of cows to study BLG's role in milk. It's thought that BLG can be removed from milk without greatly altering its properties, but its exact biological role is still a mystery. "These animals will help us to get a better idea of what this protein actually does," said Wagner.


1. Anower, J., S. Wagner, J. McCracken, D. N. Wells, and G. Laible. 2012. Targeted microRNA expression in dairy cattle directs production of β-lactoglobulin-free, high-casein milk. PNAS. Published online October 1, 2012.