Burdon, T., Laboratory of Biochemistry and Metabolism, National Institutes of Health, Bethesda, MD 20892, United States
Wall, R.J., Reproduction Laboratory, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, United States
Shamay, A., Laboratory of Biochemistry and Metabolism, National Institutes of Health, Bethesda, MD 20892, United States
Smith, G.H., Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892, United States
Hennighausen, L., Laboratory of Biochemistry and Metabolism, National Institutes of Health, Bethesda, MD 20892, United States

The whey acidic protein (WAP) gene is expressed in mammary epithelial cells at late pregnancy and throughout lactation. We have generated transgenic mice in which a mouse WAP transgene is expressed precociously in pregnancy. From 13 founder mice bearing WAP transgenes, two female founders and the daughters from a male founder failed to lactate and nurture their offspring. We named this phenotype milchlos. Mammary tissue from postpartum milchlos mice was underdeveloped, contained too few alveoli and resembled the glands of non-transgenic mid-pregnant mice. The hypothesis that alveolar development in milchlos mice was functionally arrested in a prelactational state is consistent with low levels of α-lactalbumin mRNA, and an unidentified keratin RNA in mammary tissue from postpartum mice. Defects in alveolar function in milchlos mice were detected at mid-pregnancy; in non-transgenic mice, WAP was secreted into the alveolar lumen but remained preferentially in the cytoplasm of the alveolar epithelial cells in the milchlos mice. Since deregulated WAP expression resulted in impaired mammary development, it is possible that WAP plays a regulatory role in the terminal differentiation and development of mammary alveolar cells. © 1991.