Whey acidic protein extrinsically expressed from the mouse mammary tumor virus long terminal repeat results in hyperplasia of the coagulation gland epithelium and impaired mammary development.
The whey acidic protein (WAP) is a milk protein that contains a cysteine-rich motif. This characteristic WAP signature has also been found in some protease inhibitors and certain proteins involved in tissue modeling. WAP is specifically synthesized in mammary tissue from late pregnant and lactating animals, and precocious synthesis results in impaired lobuloalveolar development of the gland in some transgenic lines. To determine whether growth modulatory effects of WAP are confined to mammary tissue, we expressed the WAP gene under the control of the mouse mammary tumor virus long terminal repeat in transgenic mice. The transgene was expressed at high levels in organs with exocrine function, such as mammary and salivary glands, prostate, seminal vesicle, and the coagulation gland. In addition to impaired mammary development, we observed hyperplasia and dysplasia of the coagulation gland epithelium. These findings suggest that WAP or a member of the WAP signature family can, in certain tissue contexts, function as an epithelial growth regulator. It appears from the present study that growth regulatory effects of WAP are restricted in the mouse to the mammary and coagulation gland epithelium.
Hennighausen
L
L
Laboratory of Biochemistry and Metabolism, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20982.
McKnight
R
R
Burdon
T
T
Baik
M
M
Wall
R J
RJ
Smith
G H
GH
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics*; D018014:Gene Transfer Techniques; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012313:RNA / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology
D017931:DNA Primers; D004279:DNA, Viral; D008894:Milk Proteins; C024471:whey acidic proteins; D012313:RNA