Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N8F?+F10 (31-DEC-07)   Donating Investigator Kenneth Korach,   LRDT, NIEHS, NIH

Description
Mice that are homozygous for this targeted allele are viable, normal in size and do not display any gross physical abnormalities. Stop codons inserted into exon 3 result in the production of truncated transcripts that are unlikely to be translated into a functional protein. Immunostaining of ovary tissue derived from homozygous females fails to detect protein product. Homozygous females are subfertile, producing fewer and smaller litters than wildtype controls. Decreased numbers of oocytes are also produced in response to superovulation (6 compared to 33.7 in wildtype controls). Male homozygotes are fertile and present no marked abnormalities other than epithelial hyperplasia in the bladder wall and prostatic collecting ducts. This mutant mouse strain may be useful in studies related to discerning the physiological roles of the estrogen signaling system.

Development
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to introduce stop codons into exon 3. The construct was introduced into 129P2/OlaHsd-derived E14TG2a embryonic stem (ES) cells (BK4 subline). Correctly targeted ES cells were injected into C57BL/6J blastocysts to obtain chimeric animals.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Esr2^tm1Unc/Esr2^tm1Unc

        involves: 129P2/OlaHsd * C57BL/6J

• reproductive system phenotype
• decreased litter size (MGI Ref ID J:51663)
  • smaller and fewer litters than controls
• prostate gland hyperplasia (MGI Ref ID J:51663)
  • observed in males greater than 3 months of age
• cardiovascular system phenotype
• abnormal vascular smooth muscle morphology (MGI Ref ID J:73898)
  • vascular smooth muscle cells are half normal size
• increased blood pressure (MGI Ref ID J:73898)
  • increased blood pressure in most mice at 6-7 months of age
  • blood pressure remains elevated to 22 months of age
  • heart rate unchanged
• increased vasoconstriction (MGI Ref ID J:73898)
• muscle phenotype
• abnormal muscle electrophysiology (MGI Ref ID J:73898)
  • absence of voltage dependent outward current in vascular smooth muscle cells
• abnormal vascular smooth muscle morphology (MGI Ref ID J:73898)
  • vascular smooth muscle cells are half normal size
• abnormal vascular smooth muscle physiology (MGI Ref ID J:73898)
  • absence of voltage dependent outward current
• nervous system phenotype
• abnormal astrocyte morphology (MGI Ref ID J:67862)
  • males had hypertrophic astroglial cells
• abnormal cerebral cortex morphology (MGI Ref ID J:67862)
  • at 2 months of age, hypocellularity of the neocortex, with severe neuronal deficit in layers II, III, IV and V; area ranged from somatosensory region to parietal region
  • at 1 year, hypocellularity in the same regions evident
  • at 2 years, thinning of layers IV and V most prominent; reduction in number and size of neurons in layer II-III and layer V
• abnormal cochlear IHC afferent innervation (MGI Ref ID J:108892)
  • at 2-6 months of age, female homozygotes exhibit some dilated afferent nerve endings on the cochlear IHCs, in the absence of a swollen stria vascularis
  • however, middle and inner ear morphology is relatively normal relative to heterozygotes, and positive estrogen receptor alpha immunostaining is noted at the same locations as in control CBA/Ca mice
• decreased brain size (MGI Ref ID J:67862)
  • at 2 years of age, brains are significantly smaller
  • atrophy most evident in somatosensory-parietal cortex
• endocrine/exocrine gland phenotype
• prostate gland hyperplasia (MGI Ref ID J:51663)
  • observed in males greater than 3 months of age
• renal/urinary system phenotype
• urinary bladder hypoplasia (MGI Ref ID J:51663)
  • observed in males greater than 3 months of age
• hearing/vestibular/ear phenotype
• abnormal cochlear IHC afferent innervation (MGI Ref ID J:108892)
  • at 2-6 months of age, female homozygotes exhibit some dilated afferent nerve endings on the cochlear IHCs, in the absence of a swollen stria vascularis
  • however, middle and inner ear morphology is relatively normal relative to heterozygotes, and positive estrogen receptor alpha immunostaining is noted at the same locations as in control CBA/Ca mice

Esr2^tm1Unc/Esr2^tm1Unc

        involves: 129P2/OlaHsd * C57BL/6

• homeostasis/metabolism phenotype
• increased circulating luteinizing hormone level (MGI Ref ID J:118736)
  • higher than normal luteinizing hormone levels are further elevated by ovariectomy

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Esr2^tm1Unc related

Endocrine Deficiency Research
Gonad Defects

Internal/Organ Research
Bladder
Prostate

Reproductive Biology Research
Endocrine Deficiencies Affecting Gonads
Fertility Defects (females only)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Esr2tm1Unc
Allele Name		targeted mutation, University of North Carolina
Allele Type		Targeted (knock-out)
Common Name(s)		BERKO; BERKOChapel Hill; ERbeta-; Erb-; beta-ERKO; betaERKO;
Mutation Made By		Kenneth Korach,   LRDT, NIEHS, NIH
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		BK4
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Esr2, estrogen receptor 2 (beta)
Chromosome		12
Gene Common Name(s)		ER beta; ER-BETA; ERbeta; ESR-BETA; ESRB; ESTRB; Erb; Erb2; Estrb; NR3A2; estrogen receptor beta; oestrogen receptor beta;
General Note		ES cell line = BK4, which is derived from a subclone of E14TG2a.
Molecular Note		A neomycin resistance cassette was inserted into exon 3 of the gene, introducing a stop codon and resulting in premature termination of translation of the Esr2 mRNA. Immunocytochemistry of ovary from homozygous mutant females showed no detectable Esr2 protein. [MGI Ref ID J:51663]

Genotyping

Genotyping Information

Genotyping Protocols

Esr2^tm1Unc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Krege JH; Hodgin JB; Couse JF; Enmark E; Warner M; Mahler JF; Sar M; Korach KS; Gustafsson JA; Smithies O. 1998. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci U S A 95(26):15677-82. [PubMed: 9861029]  [MGI Ref ID J:51663]

Additional References

Esr2^tm1Unc related

Abraham IM; Todman MG; Korach KS; Herbison AE. 2004. Critical in vivo roles for classical estrogen receptors in rapid estrogen actions on intracellular signaling in mouse brain. Endocrinology 145(7):3055-61. [PubMed: 14976146]  [MGI Ref ID J:105631]

Barros RP; Machado UF; Warner M; Gustafsson JA. 2006. Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha. Proc Natl Acad Sci U S A 103(5):1605-8. [PubMed: 16423895]  [MGI Ref ID J:105982]

Borzychowski AM; Chantakru S; Minhas K; Paffaro VA; Yamada AT; He H; Korach KS; Croy BA. 2003. Functional analysis of murine uterine natural killer cells genetically devoid of oestrogen receptors. Placenta 24(4):403-11. [PubMed: 12657515]  [MGI Ref ID J:117832]

Bryzgalova G; Gao H; Ahren B; Zierath JR; Galuska D; Steiler TL; Dahlman-Wright K; Nilsson S; Gustafsson JA; Efendic S; Khan A. 2006. Evidence that oestrogen receptor-alpha plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver. Diabetologia 49(3):588-97. [PubMed: 16463047]  [MGI Ref ID J:107888]

Burns KH; Agno JE; Chen L; Haupt B; Ogbonna SC; Korach KS; Matzuk MM. 2003. Sexually dimorphic roles of steroid hormone receptor signaling in gonadal tumorigenesis. Mol Endocrinol 17(10):2039-52. [PubMed: 12855748]  [MGI Ref ID J:84989]

Carey MA; Card JW; Bradbury JA; Moorman MP; Haykal-Coates N; Gavett SH; Graves JP; Walker VR; Flake GP; Voltz JW; Zhu D; Jacobs ER; Dakhama A; Larsen GL; Loader JE; Gelfand EW; Germolec DR; Korach KS; Zeldin DC. 2007. Spontaneous airway hyperresponsiveness in estrogen receptor-alpha-deficient mice. Am J Respir Crit Care Med 175(2):126-35. [PubMed: 17095746]  [MGI Ref ID J:135930]

Carreras E; Turner S; Paharkova-Vatchkova V; Mao A; Dascher C; Kovats S. 2008. Estradiol acts directly on bone marrow myeloid progenitors to differentially regulate GM-CSF or Flt3 ligand-mediated dendritic cell differentiation. J Immunol 180(2):727-38. [PubMed: 18178810]  [MGI Ref ID J:130951]

Chagin AS; Lindberg MK; Andersson N; Moverare S; Gustafsson JA; Savendahl L; Ohlsson C. 2004. Estrogen receptor-beta inhibits skeletal growth and has the capacity to mediate growth plate fusion in female mice. J Bone Miner Res 19(1):72-7. [PubMed: 14753739]  [MGI Ref ID J:111108]

Cheng G; Weihua Z; Makinen S; Makela S; Saji S; Warner M; Gustafsson JA; Hovatta O. 2002. A role for the androgen receptor in follicular atresia of estrogen receptor beta knockout mouse ovary. Biol Reprod 66(1):77-84. [PubMed: 11751267]  [MGI Ref ID J:74014]

Cheng G; Weihua Z; Warner M; Gustafsson JA. 2004. Estrogen receptors ER alpha and ER beta in proliferation in the rodent mammary gland. Proc Natl Acad Sci U S A 101(11):3739-46. [PubMed: 14762170]  [MGI Ref ID J:88911]

Choleris E; Gustafsson JA; Korach KS; Muglia LJ; Pfaff DW; Ogawa S. 2003. An estrogen-dependent four-gene micronet regulating social recognition: a study with oxytocin and estrogen receptor-alpha and -beta knockout mice. Proc Natl Acad Sci U S A 100(10):6192-7. [PubMed: 12730370]  [MGI Ref ID J:83406]

Choleris E; Ogawa S; Kavaliers M; Gustafsson JA; Korach KS; Muglia LJ; Pfaff DW. 2006. Involvement of estrogen receptor alpha, beta and oxytocin in social discrimination: A detailed behavioral analysis with knockout female mice. Genes Brain Behav 5(7):528-39. [PubMed: 17010099]  [MGI Ref ID J:126499]

Couse JF; Curtis Hewitt S; Korach KS. 2000. Receptor null mice reveal contrasting roles for estrogen receptor alpha and beta in reproductive tissues. J Steroid Biochem Mol Biol 74(5):287-96. [PubMed: 11162937]  [MGI Ref ID J:66741]

Couse JF; Hewitt SC; Bunch DO; Sar M; Walker VR; Davis BJ; Korach KS. 1999. Postnatal sex reversal of the ovaries in mice lacking estrogen receptors alpha and beta. Science 286(5448):2328-31. [PubMed: 10600740]  [MGI Ref ID J:59105]

Couse JF; Yates MM; Deroo BJ; Korach KS. 2005. Estrogen receptor-beta is critical to granulosa cell differentiation and the ovulatory response to gonadotropins. Endocrinology 146(8):3247-62. [PubMed: 15831568]  [MGI Ref ID J:129823]

Couse JF; Yates MM; Sanford R; Nyska A; Nilson JH; Korach KS. 2004. Formation of cystic ovarian follicles associated with elevated luteinizing hormone requires estrogen receptor-beta. Endocrinology 145(10):4693-702. [PubMed: 15231698]  [MGI Ref ID J:92628]

Couse JF; Yates MM; Walker VR; Korach KS. 2003. Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta. Mol Endocrinol 17(6):1039-53. [PubMed: 12624116]  [MGI Ref ID J:83626]

Cruz MN; Douglas G; Gustafsson JA; Poston L; Kublickiene K. 2006. Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-beta knockout mice. Am J Physiol Heart Circ Physiol 290(2):H823-9. [PubMed: 16183727]  [MGI Ref ID J:106720]

Day M; Sung A; Logue S; Bowlby M; Arias R. 2005. Beta estrogen receptor knockout (BERKO) mice present attenuated hippocampal CA1 long-term potentiation and related memory deficits in contextual fear conditioning. Behav Brain Res 164(1):128-31. [PubMed: 16054246]  [MGI Ref ID J:115451]

Dorling AA; Todman MG; Korach KS; Herbison AE. 2003. Critical role for estrogen receptor alpha in negative feedback regulation of gonadotropin-releasing hormone mRNA expression in the female mouse. Neuroendocrinology 78(4):204-9. [PubMed: 14583652]  [MGI Ref ID J:118736]

Douglas G; Cruz MN; Poston L; Gustafsson JA; Kublickiene K. 2008. Functional characterization and sex differences in small mesenteric arteries of the estrogen receptor-beta knockout mouse. Am J Physiol Regul Integr Comp Physiol 294(1):R112-20. [PubMed: 17959706]  [MGI Ref ID J:131226]

Dupont S; Dennefeld C; Krust A; Chambon P; Mark M. 2003. Expression of Sox9 in granulosa cells lacking the estrogen receptors, ERalpha and ERbeta. Dev Dyn 226(1):103-6. [PubMed: 12508230]  [MGI Ref ID J:107788]

Emmen JM; Couse JF; Elmore SA; Yates MM; Kissling GE; Korach KS. 2005. In vitro growth and ovulation of follicles from ovaries of estrogen receptor (ER){alpha} and ER{beta} null mice indicate a role for ER{beta} in follicular maturation. Endocrinology 146(6):2817-26. [PubMed: 15731357]  [MGI Ref ID J:109466]

Erlandsson MC; Jonsson CA; Islander U; Ohlsson C; Carlsten H. 2003. Oestrogen receptor specificity in oestradiol-mediated effects on B lymphopoiesis and immunoglobulin production in male mice. Immunology 108(3):346-51. [PubMed: 12603601]  [MGI Ref ID J:82423]

Erlandsson MC; Ohlsson C; Gustafsson JA; Carlsten H. 2001. Role of oestrogen receptors alpha and beta in immune organ development and in oestrogen-mediated effects on thymus. Immunology 103(1):17-25. [PubMed: 11380688]  [MGI Ref ID J:110416]

Fan X; Kim HJ; Warner M; Gustafsson JA. 2007. Estrogen receptor beta is essential for sprouting of nociceptive primary afferents and for morphogenesis and maintenance of the dorsal horn interneurons. Proc Natl Acad Sci U S A 104(34):13696-701. [PubMed: 17693550]  [MGI Ref ID J:124101]

Fan X; Warner M; Gustafsson JA. 2006. Estrogen receptor beta expression in the embryonic brain regulates development of calretinin-immunoreactive GABAergic interneurons. Proc Natl Acad Sci U S A 103(51):19338-43. [PubMed: 17159139]  [MGI Ref ID J:118243]

Forster C; Kietz S; Hultenby K; Warner M; Gustafsson JA. 2004. Characterization of the ERbeta-/-mouse heart. Proc Natl Acad Sci U S A 101(39):14234-9. [PubMed: 15375213]  [MGI Ref ID J:93438]

Forster C; Makela S; Warri A; Kietz S; Becker D; Hultenby K; Warner M; Gustafsson JA. 2002. Involvement of estrogen receptor beta in terminal differentiation of mammary gland epithelium. Proc Natl Acad Sci U S A 99(24):15578-83. [PubMed: 12438700]  [MGI Ref ID J:125583]

Fugger HN; Foster TC; Gustafsson J; Rissman EF. 2000. Novel effects of estradiol and estrogen receptor alpha and beta on cognitive function(1) Brain Res 883(2):258-64. [PubMed: 11074057]  [MGI Ref ID J:65785]

Gabel SA; Walker VR; London RE; Steenbergen C; Korach KS; Murphy E. 2005. Estrogen receptor beta mediates gender differences in ischemia/reperfusion injury. J Mol Cell Cardiol 38(2):289-97. [PubMed: 15698835]  [MGI Ref ID J:101968]

Glenmark B; Nilsson M; Gao H; Gustafsson JA; Dahlman-Wright K; Westerblad H. 2004. Difference in skeletal muscle function in males vs. females: role of estrogen receptor-beta. Am J Physiol Endocrinol Metab 287(6):E1125-31. [PubMed: 15280152]  [MGI Ref ID J:95398]

Gould ML; Hurst PR; Nicholson HD. 2007. The effects of oestrogen receptors {alpha} and {beta} on testicular cell number and steroidogenesis in mice. Reproduction 134(2):271-9. [PubMed: 17660237]  [MGI Ref ID J:123340]

Grummer R; Hewitt SW; Traub O; Korach KS; Winterhager E. 2004. Different regulatory pathways of endometrial connexin expression: preimplantation hormonal-mediated pathway versus embryo implantation-initiated pathway. Biol Reprod 71(1):273-81. [PubMed: 15028626]  [MGI Ref ID J:108494]

Gu Q; Korach KS; Moss RL. 1999. Rapid action of 17beta-estradiol on kainate-induced currents in hippocampal neurons lacking intracellular estrogen receptors. Endocrinology 140(2):660-6. [PubMed: 9927291]  [MGI Ref ID J:52901]

Hewitt SC; Korach KS. 2003. Oestrogen receptor knockout mice: roles for oestrogen receptors alpha and beta in reproductive tissues. Reproduction 125(2):143-9. [PubMed: 12578528]  [MGI Ref ID J:82473]

Imamov O; Morani A; Shim GJ; Omoto Y; Thulin-Andersson C; Warner M; Gustafsson JA. 2004. Estrogen receptor beta regulates epithelial cellular differentiation in the mouse ventral prostate. Proc Natl Acad Sci U S A 101(25):9375-80. [PubMed: 15187231]  [MGI Ref ID J:91449]

Imamov O; Yakimchuk K; Morani A; Schwend T; Wada-Hiraike O; Razumov S; Warner M; Gustafsson JA. 2007. Estrogen receptor beta-deficient female mice develop a bladder phenotype resembling human interstitial cystitis. Proc Natl Acad Sci U S A 104(23):9806-9. [PubMed: 17522255]  [MGI Ref ID J:122274]

Imwalle DB; Gustafsson JA; Rissman EF. 2005. Lack of functional estrogen receptor beta influences anxiety behavior and serotonin content in female mice. Physiol Behav 84(1):157-63. [PubMed: 15642619]  [MGI Ref ID J:101943]

Inzunza J; Morani A; Cheng G; Warner M; Hreinsson J; Gustafsson JA; Hovatta O. 2007. Ovarian wedge resection restores fertility in estrogen receptor beta knockout (ERbeta-/-) mice. Proc Natl Acad Sci U S A 104(2):600-5. [PubMed: 17197418]  [MGI Ref ID J:119080]

Islander U; Erlandsson MC; Chavoshi T; Jochems C; Moverare S; Nilsson S; Ohlsson C; Gustafsson JA; Carlsten H. 2005. Estren-mediated inhibition of T lymphopoiesis is estrogen receptor-independent whereas its suppression of T cell-mediated inflammation is estrogen receptor-dependent. Clin Exp Immunol 139(2):210-5. [PubMed: 15654819]  [MGI Ref ID J:95690]

Islander U; Erlandsson MC; Hasseus B; Jonsson CA; Ohlsson C; Gustafsson JA; Dahlgren U; Carlsten H. 2003. Influence of oestrogen receptor alpha and beta on the immune system in aged female mice. Immunology 110(1):149-57. [PubMed: 12941152]  [MGI Ref ID J:113638]

Karas RH; Schulten H; Pare G; Aronovitz MJ; Ohlsson C; Gustafsson JA; Mendelsohn ME. 2001. Effects of estrogen on the vascular injury response in estrogen receptor alpha, beta (double) knockout mice. Circ Res 89(6):534-9. [PubMed: 11557741]  [MGI Ref ID J:115411]

Korach KS. 2000. Estrogen receptor knock-out mice: molecular and endocrine phenotypes J Soc Gynecol Investig 7(1 Suppl):S16-7. [PubMed: 10732323]  [MGI Ref ID J:61234]

Korach KS; Emmen JM; Walker VR; Hewitt SC; Yates M; Hall JM; Swope DL; Harrell JC; Couse JF. 2003. Update on animal models developed for analyses of estrogen receptor biological activity. J Steroid Biochem Mol Biol 86(3-5):387-91. [PubMed: 14623535]  [MGI Ref ID J:86741]

Korte T; Fuchs M; Arkudas A; Geertz S; Meyer R; Gardiwal A; Klein G; Niehaus M; Krust A; Chambon P; Drexler H; Fink K; Grohe C. 2005. Female mice lacking estrogen receptor beta display prolonged ventricular repolarization and reduced ventricular automaticity after myocardial infarction. Circulation 111(18):2282-90. [PubMed: 15867180]  [MGI Ref ID J:111628]

Kudwa AE; Bodo C; Gustafsson JA; Rissman EF. 2005. A previously uncharacterized role for estrogen receptor beta: defeminization of male brain and behavior. Proc Natl Acad Sci U S A 102(12):4608-12. [PubMed: 15761056]  [MGI Ref ID J:97283]

Kudwa AE; Rissman EF. 2003. Double oestrogen receptor alpha and beta knockout mice reveal differences in neural oestrogen-mediated progestin receptor induction and female sexual behaviour. J Neuroendocrinol 15(10):978-83. [PubMed: 12969243]  [MGI Ref ID J:103568]

Kurita T; Lee K; Saunders PT; Cooke PS; Taylor JA; Lubahn DB; Zhao C; Makela S; Gustafsson JA; Dahiya R; Cunha GR. 2001. Regulation of progesterone receptors and decidualization in uterine stroma of the estrogen receptor-alpha knockout mouse. Biol Reprod 64(1):272-83. [PubMed: 11133684]  [MGI Ref ID J:68452]

Lambert KC; Curran EM; Judy BM; Lubahn DB; Estes DM. 2004. Estrogen receptor-alpha deficiency promotes increased TNF-alpha secretion and bacterial killing by murine macrophages in response to microbial stimuli in vitro. J Leukoc Biol 75(6):1166-72. [PubMed: 15020652]  [MGI Ref ID J:90478]

Lee KC; Jessop H; Suswillo R; Zaman G; Lanyon LE. 2004. The adaptive response of bone to mechanical loading in female transgenic mice is deficient in the absence of oestrogen receptor-alpha and -beta. J Endocrinol 182(2):193-201. [PubMed: 15283680]  [MGI Ref ID J:91765]

Liang M; Ekblad E; Gustafsson JA; Nilsson BO. 2001. Stimulation of vascular protein synthesis by activation of oestrogen receptor beta. J Endocrinol 171(3):417-23. [PubMed: 11739007]  [MGI Ref ID J:118401]

Liang M; Ekblad E; Lydrup ML; Nilsson BO. 2003. Combined lack of estrogen receptors alpha and beta affects vascular iNOS protein expression. Cell Tissue Res 313(1):63-70. [PubMed: 12827494]  [MGI Ref ID J:105095]

Lindberg MK; Alatalo SL; Halleen JM; Mohan S; Gustafsson JA JA; Ohlsson C. 2001. Estrogen receptor specificity in the regulation of the skeleton in female mice. J Endocrinol 171(2):229-36. [PubMed: 11691642]  [MGI Ref ID J:72536]

Lindberg MK; Moverare S; Skrtic S; Alatalo S; Halleen J; Mohan S; Gustafsson JA; Ohlsson C. 2002. Two different pathways for the maintenance of trabecular bone in adult male mice. J Bone Miner Res 17(4):555-62. [PubMed: 11918213]  [MGI Ref ID J:112374]

Liu F; Day M; Muniz LC; Bitran D; Arias R; Revilla-Sanchez R; Grauer S; Zhang G; Kelley C; Pulito V; Sung A; Mervis RF; Navarra R; Hirst WD; Reinhart PH; Marquis KL; Moss SJ; Pangalos MN; Brandon NJ. 2008. Activation of estrogen receptor-beta regulates hippocampal synaptic plasticity and improves memory. Nat Neurosci 11(3):334-43. [PubMed: 18297067]  [MGI Ref ID J:135696]

Luksha L; Poston L; Gustafsson JA; Aghajanova L; Kublickiene K. 2005. Gender-specific alteration of adrenergic responses in small femoral arteries from estrogen receptor-beta knockout mice. Hypertension 46(5):1163-8. [PubMed: 16216990]  [MGI Ref ID J:116826]

Massaro D; Clerch LB; Massaro GD. 2007. Estrogen receptor-alpha regulates pulmonary alveolar loss and regeneration in female mice: morphometric and gene expression studies. Am J Physiol Lung Cell Mol Physiol 293(1):L222-8. [PubMed: 17449797]  [MGI Ref ID J:125845]

Massaro D; Massaro GD. 2006. Estrogen receptor regulation of pulmonary alveolar dimensions: alveolar sexual dimorphism in mice. Am J Physiol Lung Cell Mol Physiol 290(5):L866-70. [PubMed: 16361355]  [MGI Ref ID J:115776]

Massaro D; Massaro GD. 2004. Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice. Am J Physiol Lung Cell Mol Physiol 287(6):L1154-9. [PubMed: 15298854]  [MGI Ref ID J:108147]

Meltser I; Tahera Y; Simpson E; Hultcrantz M; Charitidi K; Gustafsson JA; Canlon B. 2008. Estrogen receptor beta protects against acoustic trauma in mice. J Clin Invest 118(4):1563-70. [PubMed: 18317592]  [MGI Ref ID J:135833]

Morani A; Barros RP; Imamov O; Hultenby K; Arner A; Warner M; Gustafsson JA. 2006. Lung dysfunction causes systemic hypoxia in estrogen receptor beta knockout (ERbeta-/-) mice. Proc Natl Acad Sci U S A 103(18):7165-9. [PubMed: 16636272]  [MGI Ref ID J:109456]

Morissette M; Jourdain S; Al Sweidi S; Menniti FS; Ramirez AD; Di Paolo T. 2007. Role of estrogen receptors in neuroprotection by estradiol against MPTP toxicity. Neuropharmacology 52(7):1509-20. [PubMed: 17420033]  [MGI Ref ID J:124564]

Moverare S; Lindberg MK; Faergemann J; Gustafsson JA; Ohlsson C. 2002. Estrogen receptor alpha, but not estrogen receptor beta, is involved in the regulation of the hair follicle cycling as well as the thickness of epidermis in male mice. J Invest Dermatol 119(5):1053-8. [PubMed: 12445192]  [MGI Ref ID J:80752]

Nilsson BO; Ekblad E; Heine T; Gustafsson J. 2000. Increased magnitude of relaxation to oestrogen in aorta from oestrogen receptor beta knock-out mice. J Endocrinol 166(2):R5-9. [PubMed: 10927637]  [MGI Ref ID J:64165]

Nomura M; Akama KT; Alves SE; Korach KS; Gustafsson JA; Pfaff DW; Ogawa S. 2005. Differential distribution of estrogen receptor (ER)-alpha and ER-beta in the midbrain raphe nuclei and periaqueductal gray in male mouse: Predominant role of ER-beta in midbrain serotonergic systems. Neuroscience 130(2):445-56. [PubMed: 15664701]  [MGI Ref ID J:105156]

Nomura M; Andersson S; Korach KS; Gustafsson JA; Pfaff DW; Ogawa S. 2006. Estrogen receptor-beta gene disruption potentiates estrogen-inducible aggression but not sexual behaviour in male mice. Eur J Neurosci 23(7):1860-8. [PubMed: 16623843]  [MGI Ref ID J:108066]

Ogawa S; Chan J; Chester AE; Gustafsson JA; Korach KS; Pfaff DW. 1999. Survival of reproductive behaviors in estrogen receptor beta gene-deficient (betaERKO) male and female mice. Proc Natl Acad Sci U S A 96(22):12887-92. [PubMed: 10536018]  [MGI Ref ID J:120164]

Ogawa S; Chan J; Gustafsson JA; Korach KS; Pfaff DW. 2003. Estrogen increases locomotor activity in mice through estrogen receptor alpha: specificity for the type of activity. Endocrinology 144(1):230-9. [PubMed: 12488349]  [MGI Ref ID J:115540]

Ogawa S; Chester AE; Hewitt SC; Walker VR; Gustafsson JA; Smithies O; Korach KS; Pfaff DW. 2000. From the cover: abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta (alpha beta ERKO) Proc Natl Acad Sci U S A 97(26):14737-41. [PubMed: 11114183]  [MGI Ref ID J:66582]

Ohlsson C; Hellberg N; Parini P; Vidal O; Bohlooly M; Rudling M; Lindberg MK; Warner M; Angelin B; Gustafsson JA. 2000. Obesity and disturbed lipoprotein profile in estrogen receptor-alpha-deficient male mice Biochem Biophys Res Commun 278(3):640-5. [PubMed: 11095962]  [MGI Ref ID J:66077]

Ohnemus U; Uenalan M; Conrad F; Handjiski B; Mecklenburg L; Nakamura M; Inzunza J; Gustafsson JA; Paus R. 2005. Hair cycle control by estrogens: catagen induction via estrogen receptor (ER)-alpha is checked by ER beta signaling. Endocrinology 146(3):1214-25. [PubMed: 15591132]  [MGI Ref ID J:107589]

Omoto Y; Imamov O; Warner M; Gustafsson JA. 2005. Estrogen receptor alpha and imprinting of the neonatal mouse ventral prostate by estrogen. Proc Natl Acad Sci U S A 102(5):1484-9. [PubMed: 15665095]  [MGI Ref ID J:96107]

Patisaul HB; Scordalakes EM; Young LJ; Rissman EF. 2003. Oxytocin, but not oxytocin receptor, is rRegulated by oestrogen receptor beta in the female mouse hypothalamus. J Neuroendocrinol 15(8):787-93. [PubMed: 12834440]  [MGI Ref ID J:103579]

Patrone C; Cassel TN; Pettersson K; Piao YS; Cheng G; Ciana P; Maggi A; Warner M; Gustafsson JA; Nord M. 2003. Regulation of postnatal lung development and homeostasis by estrogen receptor beta. Mol Cell Biol 23(23):8542-52. [PubMed: 14612399]  [MGI Ref ID J:89974]

Pelzer T; Loza PA; Hu K; Bayer B; Dienesch C; Calvillo L; Couse JF; Korach KS; Neyses L; Ertl G. 2005. Increased mortality and aggravation of heart failure in estrogen receptor-beta knockout mice after myocardial infarction. Circulation 111(12):1492-8. [PubMed: 15781739]  [MGI Ref ID J:108991]

Polanczyk M; Yellayi S; Zamora A; Subramanian S; Tovey M; Vandenbark AA; Offner H; Zachary JF; Fillmore PD; Blankenhorn EP; Gustafsson JA; Teuscher C. 2004. Estrogen receptor-1 (Esr1) and -2 (Esr2) regulate the severity of clinical experimental allergic encephalomyelitis in male mice. Am J Pathol 164(6):1915-24. [PubMed: 15161628]  [MGI Ref ID J:91109]

Polanczyk MJ; Hopke C; Vandenbark AA; Offner H. 2007. Treg suppressive activity involves estrogen-dependent expression of programmed death-1 (PD-1). Int Immunol 19(3):337-43. [PubMed: 17267414]  [MGI Ref ID J:118673]

Prins GS; Birch L; Couse JF; Choi I; Katzenellenbogen B; Korach KS. 2001. Estrogen imprinting of the developing prostate gland is mediated through stromal estrogen receptor alpha: studies with alphaERKO and betaERKO mice. Cancer Res 61(16):6089-97. [PubMed: 11507058]  [MGI Ref ID J:71197]

Risbridger G; Wang H; Young P; Kurita T; Wang YZ; Lubahn D; Gustafsson JA; Cunha G. 2001. Evidence that epithelial and mesenchymal estrogen receptor-alpha mediates effects of estrogen on prostatic epithelium. Dev Biol 229(2):432-42. [PubMed: 11150243]  [MGI Ref ID J:110625]

Rissman EF; Heck AL; Leonard JE; Shupnik MA; Gustafsson JA. 2002. Disruption of estrogen receptor beta gene impairs spatial learning in female mice. Proc Natl Acad Sci U S A 99(6):3996-4001. [PubMed: 11891272]  [MGI Ref ID J:75472]

Rocha BA; Fleischer R; Schaeffer JM; Rohrer SP; Hickey GJ. 2005. 17 Beta-estradiol-induced antidepressant-like effect in the forced swim test is absent in estrogen receptor-beta knockout (BERKO) mice. Psychopharmacology (Berl) 179(3):637-43. [PubMed: 15645223]  [MGI Ref ID J:114267]

Rosenfeld CS; Cooke PS; Welsh TH Jr; Simmer G; Hufford MG; Gustafsson JA; Hess RA; Lubahn DB. 2000. The differential fate of mesonephric tubular-derived efferent ductules in estrogen receptor-alpha knockout versus wild-type female mice. Endocrinology 141(10):3792-8. [PubMed: 11014235]  [MGI Ref ID J:108807]

Sato T; Matsumoto T; Kawano H; Watanabe T; Uematsu Y; Sekine K; Fukuda T; Aihara K; Krust A; Yamada T; Nakamichi Y; Yamamoto Y; Nakamura T; Yoshimura K; Yoshizawa T; Metzger D; Chambon P; Kato S. 2004. Brain masculinization requires androgen receptor function. Proc Natl Acad Sci U S A 101(6):1673-8. [PubMed: 14747651]  [MGI Ref ID J:88153]

Savolainen S; Santti R; Streng T; Gustafsson JA; Harkonen P; Makela S. 2005. Sex specific expression of progesterone receptor in mouse lower urinary tract. Mol Cell Endocrinol 230(1-2):17-21. [PubMed: 15664447]  [MGI Ref ID J:104822]

Shim GJ; Wang L; Andersson S; Nagy N; Kis LL; Zhang Q; Makela S; Warner M; Gustafsson JA. 2003. Disruption of the estrogen receptor beta gene in mice causes myeloproliferative disease resembling chronic myeloid leukemia with lymphoid blast crisis. Proc Natl Acad Sci U S A 100(11):6694-9. [PubMed: 12740446]  [MGI Ref ID J:83617]

Skavdahl M; Steenbergen C; Clark J; Myers P; Demianenko T; Mao L; Rockman HA; Korach KS; Murphy E. 2005. Estrogen receptor-beta mediates male-female differences in the development of pressure overload hypertrophy. Am J Physiol Heart Circ Physiol 288(2):H469-76. [PubMed: 15374829]  [MGI Ref ID J:96155]

Stenberg AE; Wang H; Sahlin L; Stierna P; Enmark E; Hultcrantz M. 2002. Estrogen receptors alpha and beta in the inner ear of the 'Turner mouse' and an estrogen receptor beta knockout mouse. Hear Res 166(1-2):1-8. [PubMed: 12062753]  [MGI Ref ID J:108892]

Susiarjo M; Hassold TJ; Freeman E; Hunt PA. 2007. Bisphenol A Exposure In Utero Disrupts Early Oogenesis in the Mouse. PLoS Genet 3(1):e5. [PubMed: 17222059]  [MGI Ref ID J:120279]

Svenson JL; EuDaly J; Ruiz P; Korach KS; Gilkeson GS. 2008. Impact of estrogen receptor deficiency on disease expression in the NZM2410 lupus prone mouse. Clin Immunol 128(2):259-68. [PubMed: 18514033]  [MGI Ref ID J:137724]

Temple JL; Scordalakes EM; Bodo C; Gustafsson JA; Rissman EF. 2003. Lack of functional estrogen receptor beta gene disrupts pubertal male sexual behavior. Horm Behav 44(5):427-34. [PubMed: 14644637]  [MGI Ref ID J:102551]

Umetani M; Domoto H; Gormley AK; Yuhanna IS; Cummins CL; Javitt NB; Korach KS; Shaul PW; Mangelsdorf DJ. 2007. 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med 13(10):1185-92. [PubMed: 17873880]  [MGI Ref ID J:129931]

Vidal O; Lindberg MK; Hollberg K; Baylink DJ; Andersson G; Lubahn DB; Mohan S; Gustafsson JA; Ohlsson C. 2000. Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice. Proc Natl Acad Sci U S A 97(10):5474-9. [PubMed: 10805804]  [MGI Ref ID J:62222]

Wada-Hiraike O; Hiraike H; Okinaga H; Imamov O; Barros RP; Morani A; Omoto Y; Warner M; Gustafsson JA. 2006. Role of estrogen receptor beta in uterine stroma and epithelium: Insights from estrogen receptor beta-/- mice. Proc Natl Acad Sci U S A 103(48):18350-5. [PubMed: 17110437]  [MGI Ref ID J:117146]

Wada-Hiraike O; Imamov O; Hiraike H; Hultenby K; Schwend T; Omoto Y; Warner M; Gustafsson JA. 2006. Role of estrogen receptor (beta) in colonic epithelium Proc Natl Acad Sci U S A 103(8):2959-64. [PubMed: 16477031]  [MGI Ref ID J:107308]

Wang C; Dehghani B; Magrisso IJ; Rick EA; Bonhomme E; Cody DB; Elenich LA; Subramanian S; Murphy SJ; Kelly MJ; Rosenbaum JS; Vandenbark AA; Offner H. 2008. GPR30 Contributes to Estrogen-Induced Thymic Atrophy. Mol Endocrinol 22(3):636-48. [PubMed: 18063692]  [MGI Ref ID J:131313]

Wang L; Andersson S; Warner M; Gustafsson JA. 2003. Estrogen receptor (ER)beta knockout mice reveal a role for ERbeta in migration of cortical neurons in the developing brain. Proc Natl Acad Sci U S A 100(2):703-8. [PubMed: 12515851]  [MGI Ref ID J:81418]

Wang L; Andersson S; Warner M; Gustafsson JA. 2001. Morphological abnormalities in the brains of estrogen receptor beta knockout mice. Proc Natl Acad Sci U S A 98(5):2792-6. [PubMed: 11226319]  [MGI Ref ID J:67862]

Weihua Z; Lathe R; Warner M; Gustafsson JA. 2002. An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth. Proc Natl Acad Sci U S A 99(21):13589-94. [PubMed: 12370428]  [MGI Ref ID J:126711]

Weihua Z; Saji S; Makinen S; Cheng G; Jensen EV; Warner M; Gustafsson JA. 2000. Estrogen receptor (ER) beta, a modulator of ERalpha in the uterus. Proc Natl Acad Sci U S A 97(11):5936-41. [PubMed: 10823946]  [MGI Ref ID J:126421]

Windahl SH; Hollberg K; Vidal O; Gustafsson JA; Ohlsson C; Andersson G. 2001. Female estrogen receptor beta-/- mice are partially protected against age-related trabecular bone loss. J Bone Miner Res 16(8):1388-98. [PubMed: 11499861]  [MGI Ref ID J:112514]

Windahl SH; Vidal O; Andersson G; Gustafsson JA; Ohlsson C. 1999. Increased cortical bone mineral content but unchanged trabecular bone mineral density in female ERbeta(-/-) mice. J Clin Invest 104(7):895-901. [PubMed: 10510330]  [MGI Ref ID J:57977]

Wintermantel TM; Campbell RE; Porteous R; Bock D; Grone HJ; Todman MG; Korach KS; Greiner E; Perez CA; Schutz G; Herbison AE. 2006. Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility. Neuron 52(2):271-80. [PubMed: 17046690]  [MGI Ref ID J:117231]

Yamamoto Y; Moore R; Hess HA; Guo GL; Gonzalez FJ; Korach KS; Maronpot RR; Negishi M. 2006. Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity. J Biol Chem 281(24):16625-31. [PubMed: 16606610]  [MGI Ref ID J:113721]

Zhou XW; Gustafsson JA; Tanila H; Bjorkdahl C; Liu R; Winblad B; Pei JJ. 2008. Tau hyperphosphorylation correlates with reduced methylation of protein phosphatase 2A. Neurobiol Dis 31(3):386-94. [PubMed: 18586097]  [MGI Ref ID J:138611]

Zhu Y; Bian Z; Lu P; Karas RH; Bao L; Cox D; Hodgin J; Shaul PW; Thoren P; Smithies O; Gustafsson JA; Mendelsohn ME. 2002. Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta. Science 295(5554):505-8. [PubMed: 11799247]  [MGI Ref ID J:73898]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129P2 background and has been backcrossed to C57BL/6J for eight generations. In September 2001, the line was transferred to Taconic from the NIEHS and bred to C57BL/6NTac from which homozygotes were generated. The line is maintained by breeding heterozygous females to homozygous males.
Mating System	Heterozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.