title: STAT5 plays a critical role in regulating the 5'-flanking region of the porcine whey acidic protein gene in transgenic mice.
abstract: 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 (pWAP) 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 pWAP 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 pWAP in vivo, we generated transgenic mice expressing human recombinant granulocyte colony stimulating factor (hCSF2) in the mammary gland under the control of the pWAP 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 pWAP promoter may be useful for confining the expression of foreign proteins to the mammary gland, where they can be secreted along with milk.
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Ji
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.|Department of Animal Resource and Science, Dankook University, Cheonan, Choongnam, Republic of Korea.
authors.forename: Sang In
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Ye-Jin
authors.initials: YJ
authors.lastname: Jang
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Mi-Hyang
authors.initials: MH
authors.lastname: Jeon
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Jeom Sun
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Kyung-Woon
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Park
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Jae Gyu
authors.initials: JG
authors.lastname: Yoo
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Ik-Soo
authors.initials: IS
authors.lastname: Jeon
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Dae-Jin
authors.initials: DJ
authors.lastname: Kwon
authors.affiliation: College of Animal Life Sciences, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Choon-Keun
authors.initials: CK
authors.lastname: Park
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500, Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.
authors.forename: Sung June
authors.initials: SJ
authors.lastname: Byun
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D007774:Lactation; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008892:Milk / Q000378:metabolism*; D008894:Milk Proteins / Q000096:biosynthesis* / Q000235:genetics; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine
chemical_list: D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C024471:whey acidic proteins
keywords: STAT5; hCSF2; porcine WAP; transgenic mouse