The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Generation and reproductive phenotypes of mice lacking estrogen receptor β
Open accessAbstract
Estrogens influence the differentiation and maintenance of reproductive tissues and affect lipid metabolism and bone remodeling. Two estrogen receptors (ERs) have been identified to date, ERα and ERβ. We previously generated and studied knockout mice lacking estrogen receptor α and reported severe reproductive and behavioral phenotypes including complete infertility of both male and female mice and absence of breast tissue development. Here we describe the generation of mice lacking estrogen receptor β (ERβ −/−) by insertion of a neomycin resistance gene into exon 3 of the coding gene by using homologous recombination in embryonic stem cells. Mice lacking this receptor develop normally and are indistinguishable grossly and histologically as young adults from their littermates. RNA analysis and immunocytochemistry show that tissues from ERβ −/− mice lack normal ERβ RNA and protein. Breeding experiments with young, sexually mature females show that they are fertile and exhibit normal sexual behavior, but have fewer and smaller litters than wild-type mice. Superovulation experiments indicate that this reduction in fertility is the result of reduced ovarian efficiency. The mutant females have normal breast development and lactate normally. Young, sexually mature male mice show no overt abnormalities and reproduce normally. Older mutant males display signs of prostate and bladder hyperplasia. Our results indicate that ERβ is essential for normal ovulation efficiency but is not essential for female or male sexual differentiation, fertility, or lactation. Future experiments are required to determine the role of ERβ in bone and cardiovascular homeostasis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The nuclear receptor superfamily: the second decade
Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90199-x · Cited by 6,964
Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man
Smith, E. P., Boyd, J., Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B., & Korach, K. S. (1994) · New England Journal of Medicine · doi:10.1056/nejm199410203311604 · Cited by 2,471
Self-citationValery (1995) · doi:10.1001/jama.1995.03520270033028 · Cited by 2,320
Fisher, C. R., Graves, K. H., Parlow, A. F., & Simpson, E. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.12.6965 · Cited by 867
Cited by
Estrogen Receptor Null Mice: What Have We Learned and Where Will They Lead Us?
Couse, J. F., & Korach, K. S. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0370 · Cited by 2,045
Self-citationEstrogen receptors: how do they signal and what are their targets
Heldring, N., Pike, A., Andersson, S., Matthews, J., Cheng, G., Hartman, J., Tujague, M., Ström, A., Treuter, E., Warner, M., et al. (2007) · Physiological Reviews · doi:10.1152/physrev.00026.2006 · Cited by 1,857
Self-citationIncreased adipose tissue in male and female estrogen receptor-α knockout mice
Heine, P. A., Taylor, J. A., Iwamoto, G. A., Lubahn, D. B., & Cooke, P. S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.23.12729 · Cited by 1,282
Dupont, S., Krust, A., Gansmuller, A., Dierich, A., Chambon, P., & Mark, M. (2000) · Development · doi:10.1242/dev.127.19.4277 · Cited by 1,064
Sources of estrogen and their importance
Simpson, E. R. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00360-1 · Cited by 936
Simpson, E. R., Clyne, C., Rubin, G., Boon, W. C., Robertson, K., Britt, K., Speed, C., & Jones, M. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.081601.142703 · Cited by 773
Gillies, G. E., & McArthur, S. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002071 · Cited by 733
Vanderschueren, D., Vandenput, L., Boonen, S., Lindberg, M. K., Bouillon, R., & Ohlsson, C. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0003 · Cited by 717
Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition
Haizlip, K. M., Harrison, B. C., & Leinwand, L. A. (2015) · Physiology · doi:10.1152/physiol.00024.2014 · Cited by 521
A role for estrogen receptor β in the regulation of growth of the ventral prostate
Weihua, Z., Mäkelä, S., Andersson, L. C., Salmi, S., Saji, S., Webster, J. I., Jensen, E. V., Nilsson, S., Warner, M., & Gustafsson, J.-Å. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111150898 · Cited by 440
Self-citationCholeris, E., Gustafsson, J.-Å., Korach, K. S., Muglia, L. J., Pfaff, D. W., & Ogawa, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0631699100 · Cited by 386
Self-citationBryzgalova, G., Gao, H., Ahren, B., Zierath, J. R., Galuska, D., Steiler, T. L., Dahlman-Wright, K., Nilsson, S., Gustafsson, J.-Å., Efendic, S., et al. (2006) · Diabetologia · doi:10.1007/s00125-005-0105-3 · Cited by 384
Self-citationHan, S. J., Jung, S. Y., Wu, S.-P., Hawkins, S. M., Park, M. J., Kyo, S., Qin, J., Lydon, J. P., Tsai, S. Y., Tsai, M.-J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.10.034 · Cited by 380
Herbison, A. E. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.006 · Cited by 351
Promoter Methylation Regulates Estrogen Receptor 2 in Human Endometrium and Endometriosis1
Xue, Q., Lin, Z., Cheng, Y.-H., Huang, C.-C., Marsh, E., Yin, P., Milad, M. P., Confino, E., Reierstad, S., Innes, J., et al. (2007) · Biology of Reproduction · doi:10.1095/biolreprod.107.061804 · Cited by 346
The neurobiology of preovulatory and estradiol-induced gonadotropin-releasing hormone surges
Christian, C. A., & Moenter, S. M. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0023 · Cited by 300
Molecular Mechanisms of Estrogen Action: Selective Ligands and Receptor Pharmacology
Katzenellenbogen, B. S., Choi, I., Delage-Mourroux, R., Ediger, T. R., Martini, P. G. V., Montano, M., Sun, J., Weis, K., & Katzenellenbogen, J. A. (2000) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(00)00104-7 · Cited by 289
Estrogen—the Good, the Bad, and the Unexpected
Simpson, E. R., Misso, M., Hewitt, K. N., Hill, R. A., Boon, W. C., Jones, M. E., Kovacic, A., Zhou, J., & Clyne, C. D. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0020 · Cited by 266
Muscle GLUT4 regulation by estrogen receptors ERβ and ERα
Barros, R. P. A., Machado, U. F., Warner, M., & Gustafsson, J.-Å. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510391103 · Cited by 263
Self-citationA G-Protein-Coupled Estrogen Receptor Is Involved in Hypothalamic Control of Energy Homeostasis
Qiu, J., Bosch, M. A., Tobias, S. C., Krust, A., Graham, S. M., Murphy, S. J., Korach, K. S., Chambon, P., Scanlan, T. S., Rønnekleiv, O. K., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0327-06.2006 · Cited by 217
Self-citationEffects of estrogen on the vascular system
Tostes, R. C., Nigro, D., Fortes, Z. B., & Carvalho, M. H. C. (2003) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2003000900002 · Cited by 213
Critchley, H. O. D., Brenner, R. M., Henderson, T. A., Williams, K., Nayak, N. R., Slayden, O. D., Millar, M. R., & Saunders, P. T. K. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.3.7317 · Cited by 210
Steroids, stress and the gut microbiome-brain axis
Tetel, M. J., de Vries, G. J., Melcangi, R. C., Panzica, G., & O'Mahony, S. M. (2018) · Journal of Neuroendocrinology · doi:10.1111/jne.12548 · Cited by 187
Saunders, P. T. K., Millar, M. R., Williams, K., Macpherson, S., Harkiss, D., Anderson, R. A., Orr, B., Groome, N. P., Scobie, G., & Fraser, H. M. (2000) · Biology of Reproduction · doi:10.1095/biolreprod63.4.1098 · Cited by 175
Risks and benefits of dietary isoflavones for cancer
Andres, S., Abraham, K., Appel, K. E., & Lampen, A. (2011) · Critical Reviews in Toxicology · doi:10.3109/10408444.2010.541900 · Cited by 168
Selective estrogen receptor-β activation stimulates skeletal muscle growth and regeneration
Velders, M., Schleipen, B., Fritzemeier, K. H., Zierau, O., & Diel, P. (2012) · The FASEB Journal · doi:10.1096/fj.11-194779 · Cited by 162
Patisaul, H. B., Scordalakes, E. M., Young, L. J., & Rissman, E. F. (2003) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2003.01061.x · Cited by 160
What have we learned about GPER function in physiology and disease from knockout mice
Prossnitz, E. R., & Hathaway, H. J. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.06.014 · Cited by 157
Participation of ERα and ERβ in glucose homeostasis in skeletal muscle and white adipose tissue
Barros, R. P. A., Gabbi, C., Morani, A., Warner, M., & Gustafsson, J.-Å. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00189.2009 · Cited by 155
Self-citationTrainor, B. C., Bird, I. M., Alday, N. A., Schlinger, B. A., & Marler, C. A. (2003) · Neuroendocrinology · doi:10.1159/000071704 · Cited by 147
Estrogen Receptors Modulation of Anxiety-Like Behavior
Borrow, A. P., & Handa, R. J. (2017) · Vitamins and Hormones · doi:10.1016/bs.vh.2016.08.004 · Cited by 146
Trukhacheva, E., Lin, Z., Reierstad, S., Cheng, Y.-H., Milad, M., & Bulun, S. E. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1466 · Cited by 143
A previously uncharacterized role for estrogen receptor β: Defeminization of male brain and behavior
Kudwa, A. E., Bodo, C., Gustafsson, J.-Å., & Rissman, E. F. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500752102 · Cited by 135
Self-citationTaylor, L. C., Gilmore, W., Ting, J. P. ‐., & Matsushima, G. K. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22215 · Cited by 123
Difference in skeletal muscle function in males vs. females: role of estrogen receptor-β
Glenmark, B., Nilsson, M., Gao, H., Gustafsson, J.-Å., Dahlman-Wright, K., & Westerblad, H. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00098.2004 · Cited by 121
Self-citationThe role of estrogen deficiency in skin ageing and wound healing
Emmerson, E., & Hardman, M. J. (2012) · Biogerontology · doi:10.1007/s10522-011-9322-y · Cited by 118
Role of uterine stromal-epithelial crosstalk in embryo implantation
Hantak, A. M., Bagchi, I. C., & Bagchi, M. K. (2014) · The International Journal of Developmental Biology · doi:10.1387/ijdb.130348mb · Cited by 112
Effect of estrogen deficiency in the male: the ArKO mouse model
Murata, Y., Robertson, K. M., Jones, M. E. E., & Simpson, E. R. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00090-4 · Cited by 111
Gibson, D. A., & Saunders, P. T. K. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.09.026 · Cited by 107
Estrogenic Regulation of the GnRH Neuron
Radovick, S., Levine, J. E., & Wolfe, A. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00052 · Cited by 102
A Potential Role for Estrogen in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis
OFFNER, H., & POLANCZYK, M. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1386.021 · Cited by 102
Roles for Oestrogen Receptor β in Adult Brain Function
Handa, R. J., Ogawa, S., Wang, J. M., & Herbison, A. E. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02206.x · Cited by 97
Sexual dimorphism of cardiometabolic dysfunction: Gut microbiome in the play?
Cross, T.-W. L., Kasahara, K., & Rey, F. E. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.05.016 · Cited by 87
Dworatzek, E., Mahmoodzadeh, S., Schubert, C., Westphal, C., Leber, J., Kusch, A., Kararigas, G., Fliegner, D., Moulin, M., Ventura-Clapier, R., et al. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu065 · Cited by 79
Self-citationChaban, V. V., & Micevych, P. E. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20524 · Cited by 78
Sánchez-Andrade, G., & Kendrick, K. M. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.10.016 · Cited by 72
Wang, L., & Moenter, S. M. (2020) · Neuroendocrinology · doi:10.1159/000503006 · Cited by 63
Brown, M., Ning, J., Ferreira, J. A., Bogener, J. L., & Lubahn, D. B. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90696.2008 · Cited by 60
Estrogens: Two nuclear receptors, multiple possibilities
Biason-Lauber, A., & Lang-Muritano, M. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2022.111710 · Cited by 49
Sartorius, G. A., Ly, L. P., & Handelsman, D. J. (2014) · The Journal of Sexual Medicine · doi:10.1111/jsm.12550 · Cited by 44
Remodeling of uterine innervation.
Latini, C., Frontini, A., Morroni, M., Marzioni, D., Castellucci, M., & Smith, P. G. (2008) · Cell and Tissue Research · doi:10.1007/s00441-008-0657-x · Cited by 43
The role of noradrenaline in the generation of the preovulatory LH surge in the ewe
Clarke, I. J., Scott, C. J., Pereira, A., & Pompolo, S. (2006) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2005.07.006 · Cited by 22
Gustafsson, J.-A. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0479 · Cited by 19
Self-citationNeonatal agonism of ERβ impairs male reproductive behavior and attractiveness
Sullivan, A. W., Hamilton, P., & Patisaul, H. B. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.04.006 · Cited by 19
Associations between estrogen receptor-beta polymorphisms and endometriosis risk: a meta-analysis
Guo, R., Zheng, N., Ding, S., Zheng, Y., & Feng, L. (2014) · Diagnostic Pathology · doi:10.1186/s13000-014-0184-x · Cited by 10
Ploskonka, S. D., Eaton, J. L., Carr, M. S., Schmidt, J. V., & Cushing, B. S. (2016) · Developmental Psychobiology · doi:10.1002/dev.21367 · Cited by 7
Patisaul, H., & Whitten, P. (2004) · Endocrine Disruptors · doi:10.1201/9781420038866.ch5 · Cited by 4
Metadata
- Authors
- Krege, J. H., Hodgin, J. B., Couse, J. F., Enmark, E., Warner, M., Mahler, J. F., Sar, M., Korach, K. S., Gustafsson, J.-Å., & Smithies, O.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-12-22
- Volume
- 95
- Issue
- 26
- Pages
- 15677-15682
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2012425172
- Cited by
- 1,691
- References
- 4
- FWCI
- 43.43
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.