A 470 bp WAP-promoter fragment confers lactation independent, progesterone regulated mammary-specific gene expression in transgenic mice.
The ability of a 470 bp sub-fragment of the murine whey acidic protein (WAP) promoter in the context of a retroviral expression plasmid to direct gene expression to mammary epithelial cells was analysed in a number of independent transgenic mouse lines. In contrast to previous findings with the genuine 2.5 kb promoter fragment, our studies revealed a highly mammary gland-specific expression detectable only in non-lactating animals. This suggested a mainly progesterone-regulated activity of the short fragment. Therefore, transgene expression was examined in the progesterone-determined estrous cycle and during pregnancy. In accordance with in vitro data from stably transfected cell lines, in both situations expression was upregulated at stages associated with high progesterone levels. Taken together these data provide deeper insight into WAP-promoter regulation and stress the usefulness of the shortened fragment for a lactation independent mammary-targeted expression.
Lipnik
Karoline
K
Research Institute for Virology and Biomedicine, University of Veterinary Medicine, A-1210 Vienna, Austria.
Petznek
Helga
H
Renner-Müller
Ingrid
I
Egerbacher
Monika
M
Url
Angelika
A
Salmons
Brian
B
Günzburg
Walter H
WH
Hohenadl
Christine
C
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D004847:Epithelial Cells / Q000502:physiology; D004971:Estrus / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D007774:Lactation; D008321:Mammary Glands, Animal / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000235:genetics*; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology; D011401:Promoter Regions, Genetic; D012190:Retroviridae; D014407:Tumor Cells, Cultured
D008894:Milk Proteins; C024471:whey acidic proteins; D011374:Progesterone