Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Aug;85(16):5874–5878. doi: 10.1073/pnas.85.16.5874

A milk protein gene promoter directs the expression of human tissue plasminogen activator cDNA to the mammary gland in transgenic mice.

C W Pittius 1, L Hennighausen 1, E Lee 1, H Westphal 1, E Nicols 1, J Vitale 1, K Gordon 1
PMCID: PMC281867  PMID: 2842753

Abstract

Whey acidic protein (WAP) is a major whey protein in mouse milk. Its gene is expressed in the lactating mammary gland and is inducible by steroid and peptide hormones. A series of transgenic mice containing a hybrid gene in which human tissue plasminogen activator (tPA) cDNA is under the control of the murine WAP gene promoter had previously been generated. In this study, 21 tissues from lactating and virgin transgenic female mice containing the WAP-tPA hybrid gene were screened for the distribution of murine WAP and human tPA transcripts. Like the endogenous WAP RNA, WAP-tPA RNA was expressed predominantly in mammary gland tissue and appeared to be inducible by lactation. Whereas WAP transcripts were not detected in 22 tissues of virgin mice, low levels of WAP-tPA RNA, which were not modulated during lactation, were found in tongue, kidney, and sublingual gland. These studies demonstrate that the WAP gene promoter can target the expression of a transgene to the mammary gland and that this expression is inducible during lactation.

Full text

PDF
5874

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andres A. C., Schönenberger C. A., Groner B., Hennighausen L., LeMeur M., Gerlinger P. Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1299–1303. doi: 10.1073/pnas.84.5.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campbell S. M., Rosen J. M., Hennighausen L. G., Strech-Jurk U., Sippel A. E. Comparison of the whey acidic protein genes of the rat and mouse. Nucleic Acids Res. 1984 Nov 26;12(22):8685–8697. doi: 10.1093/nar/12.22.8685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Choi Y. W., Henrard D., Lee I., Ross S. R. The mouse mammary tumor virus long terminal repeat directs expression in epithelial and lymphoid cells of different tissues in transgenic mice. J Virol. 1987 Oct;61(10):3013–3019. doi: 10.1128/jvi.61.10.3013-3019.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  7. Granelli-Piperno A., Reich E. A study of proteases and protease-inhibitor complexes in biological fluids. J Exp Med. 1978 Jul 1;148(1):223–234. doi: 10.1084/jem.148.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hennighausen L. G., Sippel A. E. Characterization and cloning of the mRNAs specific for the lactating mouse mammary gland. Eur J Biochem. 1982 Jun 15;125(1):131–141. doi: 10.1111/j.1432-1033.1982.tb06660.x. [DOI] [PubMed] [Google Scholar]
  9. Hennighausen L. G., Sippel A. E. Mouse whey acidic protein is a novel member of the family of 'four-disulfide core' proteins. Nucleic Acids Res. 1982 Apr 24;10(8):2677–2684. doi: 10.1093/nar/10.8.2677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hobbs A. A., Richards D. A., Kessler D. J., Rosen J. M. Complex hormonal regulation of rat casein gene expression. J Biol Chem. 1982 Apr 10;257(7):3598–3605. [PubMed] [Google Scholar]
  11. Khillan J. S., Schmidt A., Overbeek P. A., de Crombrugghe B., Westphal H. Developmental and tissue-specific expression directed by the alpha 2 type I collagen promoter in transgenic mice. Proc Natl Acad Sci U S A. 1986 Feb;83(3):725–729. doi: 10.1073/pnas.83.3.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Krumlauf R., Hammer R. E., Tilghman S. M., Brinster R. L. Developmental regulation of alpha-fetoprotein genes in transgenic mice. Mol Cell Biol. 1985 Jul;5(7):1639–1648. doi: 10.1128/mcb.5.7.1639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  14. Low M. J., Lechan R. M., Hammer R. E., Brinster R. L., Habener J. F., Mandel G., Goodman R. H. Gonadotroph-specific expression of metallothionein fusion genes in pituitaries of transgenic mice. Science. 1986 Feb 28;231(4741):1002–1004. doi: 10.1126/science.2868526. [DOI] [PubMed] [Google Scholar]
  15. Lubon H., Hennighausen L. Nuclear proteins from lactating mammary glands bind to the promoter of a milk protein gene. Nucleic Acids Res. 1987 Mar 11;15(5):2103–2121. doi: 10.1093/nar/15.5.2103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nicoll C. S., Tucker H. A. Estimates of parenchymal, stromal, and lymph node deoxyribonucleic acid in mammary glands of C3H/Crgl-2 mice. Life Sci. 1965 May;4(9):993–1001. doi: 10.1016/0024-3205(65)90203-1. [DOI] [PubMed] [Google Scholar]
  18. Overbeek P. A., Lai S. P., Van Quill K. R., Westphal H. Tissue-specific expression in transgenic mice of a fused gene containing RSV terminal sequences. Science. 1986 Mar 28;231(4745):1574–1577. doi: 10.1126/science.3006249. [DOI] [PubMed] [Google Scholar]
  19. Palmiter R. D., Brinster R. L. Germ-line transformation of mice. Annu Rev Genet. 1986;20:465–499. doi: 10.1146/annurev.ge.20.120186.002341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Simons J. P., McClenaghan M., Clark A. J. Alteration of the quality of milk by expression of sheep beta-lactoglobulin in transgenic mice. Nature. 1987 Aug 6;328(6130):530–532. doi: 10.1038/328530a0. [DOI] [PubMed] [Google Scholar]
  21. Sinn E., Muller W., Pattengale P., Tepler I., Wallace R., Leder P. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell. 1987 May 22;49(4):465–475. doi: 10.1016/0092-8674(87)90449-1. [DOI] [PubMed] [Google Scholar]
  22. Swift G. H., Hammer R. E., MacDonald R. J., Brinster R. L. Tissue-specific expression of the rat pancreatic elastase I gene in transgenic mice. Cell. 1984 Oct;38(3):639–646. doi: 10.1016/0092-8674(84)90258-7. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES