Skip to main content
SpringerLink
Log in

Estrogen Receptor-α Knockout Mice

  • Protocol
Estrogen Receptors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1366))

Abstract

Tissue specific knockout mice are valuable tools to study gene function in vivo. The method uses the Cre/loxP system in which loxP sites are cloned into the genome surrounding one or more exons of a gene and the targeted exon(s) are deleted when the Cre enzyme is expressed. Mouse lines that are prepared for the generation of knockout ERα mice have been developed independently by many research groups and the number of available transgenic mouse lines that express Cre under tissue specific promoters is large. Here, we describe how tissue specific ERα knockout mice are generated.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mangelsdorf DJ, Thummel C, Beato M et al (1995) The nuclear receptor superfamily: the second decade. Cell 83:835–839

    Article  CAS  Google Scholar 

  2. Nilsson S, Makela S, Treuter E et al (2001) Mechanisms of estrogen action. Physiol Rev 81:1535–1565

    Article  CAS  Google Scholar 

  3. Lubahn DB, Moyer JS, Golding TS et al (1993) Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci U S A 90:11162–11166

    Article  CAS  Google Scholar 

  4. Hewitt SC, Korach KS (2003) Oestrogen receptor knockout mice: roles for oestrogen receptors alpha and beta in reproductive tissues. Reproduction 125:143–149

    Article  CAS  Google Scholar 

  5. Bondesson M, Hao R, Lin CY et al (2014) Estrogen receptor signaling during vertebrate development. Biochim Biophys Acta 1849(2):142–151

    Article  Google Scholar 

  6. Sauer B, Henderson N (1988) Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci U S A 85:5166–5170

    Article  CAS  Google Scholar 

  7. Gu H, Marth JD, Orban PC et al (1994) Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science 265:103–106

    Article  CAS  Google Scholar 

  8. Dupont S, Krust A, Gansmuller A et al (2000) Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes. Development 127:4277–4291

    CAS  PubMed  Google Scholar 

  9. Wintermantel TM, Campbell RE, Porteous R et al (2006) Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility. Neuron 52:271–280

    Article  CAS  Google Scholar 

  10. Feng Y, Manka D, Wagner KU, Khan SA (2007) Estrogen receptor-alpha expression in the mammary epithelium is required for ductal and alveolar morphogenesis in mice. Proc Natl Acad Sci U S A 104:14718–14723

    Article  CAS  Google Scholar 

  11. Chen M, Wolfe A, Wang X et al (2009) Generation and characterization of a complete null estrogen receptor alpha mouse using Cre/LoxP technology. Mol Cell Biochem 321:145–153

    Article  CAS  Google Scholar 

  12. Martin-Millan M, Almeida M, Ambrogini E et al (2010) The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone. Mol Endocrinol 24:323–334

    Article  CAS  Google Scholar 

  13. Hewitt SC, Kissling GE, Fieselman KE et al (2010) Biological and biochemical consequences of global deletion of exon 3 from the ER alpha gene. FASEB J 24:4660–4667

    Article  CAS  Google Scholar 

  14. Antonson P, Omoto Y, Humire P et al (2012) Generation of ERalpha-floxed and knockout mice using the Cre/LoxP system. Biochem Biophys Res Commun 424:710–716

    Article  CAS  Google Scholar 

  15. Spence RD, Hamby ME, Umeda E et al (2011) Neuroprotection mediated through estrogen receptor-alpha in astrocytes. Proc Natl Acad Sci U S A 108:8867–8872

    Article  CAS  Google Scholar 

  16. Xu Y, Nedungadi TP, Zhu L et al (2011) Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab 14:453–465

    Article  CAS  Google Scholar 

  17. Gieske MC, Kim HJ, Legan SJ et al (2008) Pituitary gonadotroph estrogen receptor-alpha is necessary for fertility in females. Endocrinology 149:20–27

    Article  CAS  Google Scholar 

  18. Singh SP, Wolfe A, Ng Y et al (2009) Impaired estrogen feedback and infertility in female mice with pituitary-specific deletion of estrogen receptor alpha (ESR1). Biol Reprod 81:488–496

    Article  CAS  Google Scholar 

  19. Winuthayanon W, Hewitt SC, Orvis GD et al (2010) Uterine epithelial estrogen receptor alpha is dispensable for proliferation but essential for complete biological and biochemical responses. Proc Natl Acad Sci U S A 107:19272–19277

    Article  CAS  Google Scholar 

  20. Laws MJ, Kannan A, Pawar S et al (2014) Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice. PLoS Genet 10:e1004230

    Article  Google Scholar 

  21. Lee S, Kang DW, Hudgins-Spivey S et al (2009) Theca-specific estrogen receptor-alpha knockout mice lose fertility prematurely. Endocrinology 150:3855–3862

    Article  CAS  Google Scholar 

  22. Chen M, Yeh CR, Chang HC et al (2012) Loss of epithelial oestrogen receptor alpha inhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models. J Pathol 226:17–27

    Article  CAS  Google Scholar 

  23. Della Torre S, Rando G, Meda C et al (2011) Amino acid-dependent activation of liver estrogen receptor alpha integrates metabolic and reproductive functions via IGF-1. Cell Metab 13:205–214

    Article  CAS  Google Scholar 

  24. Matic M, Bryzgalova G, Gao H et al (2013) Estrogen signalling and the metabolic syndrome: targeting the hepatic estrogen receptor alpha action. PLoS One 8:e57458

    Article  CAS  Google Scholar 

  25. Nakamura T, Imai Y, Matsumoto T et al (2007) Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell 130:811–823

    Article  CAS  Google Scholar 

  26. Windahl SH, Borjesson AE, Farman HH et al (2013) Estrogen receptor-alpha in osteocytes is important for trabecular bone formation in male mice. Proc Natl Acad Sci U S A 110:2294–2299

    Article  CAS  Google Scholar 

  27. Maatta JA, Buki KG, Gu G et al (2013) Inactivation of estrogen receptor alpha in bone-forming cells induces bone loss in female mice. FASEB J 27:478–488

    Article  CAS  Google Scholar 

  28. Wong WP, Tiano JP, Liu S et al (2010) Extranuclear estrogen receptor-alpha stimulates NeuroD1 binding to the insulin promoter and favors insulin synthesis. Proc Natl Acad Sci U S A 107:13057–13062

    Article  CAS  Google Scholar 

  29. Davis KE, Neinast MD, Sun K et al (2013) The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis. Mol Metab 2:227–242

    Article  CAS  Google Scholar 

  30. Antonson P, Matic M, Portwood N et al (2014) aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra. PLoS One 9:e85581

    Article  Google Scholar 

  31. Harno E, Cottrell EC, White A (2013) Metabolic pitfalls of CNS Cre-based technology. Cell Metab 18:21–28

    Article  CAS  Google Scholar 

  32. Rempe D, Vangeison G, Hamilton J et al (2006) Synapsin I Cre transgene expression in male mice produces germline recombination in progeny. Genesis 44:44–49

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a Grant from the Swedish Cancer Fund. J.-Å. G. is thankful to the Robert A. Welch Foundation for an endowment.

Author information

Authors and Affiliations

  1. Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83, Huddinge, Sweden

    Per Antonson, Patricia Humire & Jan-Åke Gustafsson

  2. Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, 77204, USA

    Jan-Åke Gustafsson

Authors
  1. Per Antonson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patricia Humire
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan-Åke Gustafsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Per Antonson .

Editor information

Editors and Affiliations

  1. University of South Dakota Sanford School of Medicine, Vermillion, South Dakota, USA

    Kathleen M. Eyster

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Antonson, P., Humire, P., Gustafsson, JÅ. (2016). Estrogen Receptor-α Knockout Mice. In: Eyster, K.M. (eds) Estrogen Receptors. Methods in Molecular Biology, vol 1366. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3127-9_33

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3127-9_33

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3126-2

  • Online ISBN: 978-1-4939-3127-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation