Wall, R.J., Biochemistry/Metabolism Lab., National Institute of Diabetes, National Institutes of Health, Bethesda, MD 20892, United States
Pursel, V.G., Biochemistry/Metabolism Lab., National Institute of Diabetes, National Institutes of Health, Bethesda, MD 20892, United States
Shamay, A., Biochemistry/Metabolism Lab., National Institute of Diabetes, National Institutes of Health, Bethesda, MD 20892, United States
McKnight, R.A., Biochemistry/Metabolism Lab., National Institute of Diabetes, National Institutes of Health, Bethesda, MD 20892, United States
Pittius, C.W., Biochemistry/Metabolism Lab., National Institute of Diabetes, National Institutes of Health, Bethesda, MD 20892, United States
Hennighausen, L., Biochemistry/Metabolism Lab., National Institute of Diabetes, National Institutes of Health, Bethesda, MD 20892, United States

The whey acidic protein (WAP) is a major milk protein in mice, rats, and rabbits but has not been found in milk of livestock including swine. To determine whether mammary gland regulatory elements from the WAP gene function across species boundaries and whether it is possible to qualitatively alter milk protein composition, we introduced the mouse WAP gene into the genome of swine. Three lines of transgenic swine were analyzed, and mouse WAP was detected in milk from all lactating females at concentrations of about 1 g/liter; these levels are similar to those found in mouse milk. Expression of the corresponding RNA was specific to the mammary gland. Our results suggest that the molecular basis of mammary-specific gene expression is conserved between swine and mouse. In addition the WAP gene must share, with other milk protein genes, elements that target gene expression to the mammary gland. Mouse WAP accounted for about 3% of the total milk proteins in transgenic pigs, thus demonstrating that it is possible to produce high levels of a foreign protein in milk of farm animals.