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STAT5 plays a critical role in regulating the 5′‐flanking region of the porcine whey acidic protein gene in transgenic mice
Author(s) -
Ji Miran,
Lee Sang In,
Jang YeJin,
Jeon Mihyang,
Kim Jeom Sun,
Kim KyungWoon,
Park JinKi,
Yoo Jae Gyu,
Jeon IkSoo,
Kwon DaeJin,
Park ChoonKeun,
Byun Sung June
Publication year - 2015
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.22535
Subject(s) - biology , transgene , 5' flanking region , gene , genetically modified mouse , microbiology and biotechnology , stat5 , genetics , gene expression , promoter
SUMMARY The mammary gland serves as a valuable bioreactor system for the production of recombinant proteins in lactating animals. Pharmaceutical‐grade recombinant protein can be harvested from the milk of transgenic animals that carry a protein of interest under the control of promoter regions genes encoding milk proteins. Whey acidic protein ( WAP ), for example, is predominantly expressed in the mammary gland and is regulated by lactating hormones during pregnancy. We cloned the 5′‐flanking region of the porcine WAP gene (p WAP ) to confirm the sequence elements in its promoter that are required for gene‐expression activity. In the present study, we investigated how lactogenic hormones—including prolactin, hydrocortisone, and insulin—contribute to the transcriptional activation of the p WAP promoter region in mammalian cells, finding that these hormones activate STAT5 signaling, which in turn induce gene expression via STAT5 binding sites in its 5′‐flanking region. To confirm the expression and hormonal regulation of the 5′‐flanking region of p WAP in vivo, we generated transgenic mice expressing human recombinant granulocyte colony stimulating factor (hCSF2) in the mammary gland under the control of the p WAP promoter. These mice secreted hCSF2 protein in their milk at levels ranging from 242 to 1,274.8 ng/ml. Collectively, our findings show that the p WAP promoter may be useful for confining the expression of foreign proteins to the mammary gland, where they can be secreted along with milk. Mol. Reprod. Dev. 82: 957–966, 2015. © 2015 Wiley Periodicals, Inc .