www.nature.com/naturebiotechnology
• FEBRUARY 2003 • VOLUME 21 • nature biotechnology
Cloned transgenic cattle produce milk with higher
levels of β-casein and κ-casein
Brigid Brophy1, Grant Smolenski1, Thomas Wheeler1, David Wells1, Phil L’Huillier1,2, and Götz Laible1*
Published online 27 January 2003; doi:10.1038/nbt783
To enhance milk composition and milk processing efficiency by increasing the casein concentration in milk,
we have introduced additional copies of the genes encoding bovine β- and κ-casein (CSN2 and CSN3,
respectively) into female bovine fibroblasts. Nuclear transfer with four independent donor cell lines resulted in
the production of 11 transgenic calves. The analysis of hormonally induced milk showed substantial expres-
sion and secretion of the transgene-derived caseins into milk. Nine cows, representing two high-expressing
lines, produced milk with an 8–20% increase in β-casein, a twofold increase in κ-casein levels, and a
markedly altered κ-casein to total casein ratio. These results show that it is feasible to substantially alter a
major component of milk in high producing dairy cows by a transgenic approach and thus to improve the
functional properties of dairy milk.
RESEARCH ARTICLE
Today, milk represents an important food source consumed not only
in its natural form, but also in a wide variety of processed products.
Milk protein, 80% of which consists of casein, is one of the most
valuable components of milk because of its nutritional value and
processing properties. Therefore, casein is a prime target for the
improvement of milk composition.
The casein fraction of bovine milk comprises four proteins (αs1-,
α s2-, β-, and κ-casein), which exist naturally in a number of protein
variants. They are aggregated into large colloidal micelles, the
structure and stability of which govern many of the complex
physicochemical properties of milk. Relatively small changes in
casein ratios can affect the micelle structure and thus can have sub-
stantial effects on the