This Esr1 mutant strain is a functional knock out of ERα. Female mice homozygous for this mutation are infertile, exhibit cystic ovaries that lack corpora lutea and hypoplastic uteri that are unresponsive to estrogen. Homozygous males show reduced testis weight associated with diminished sperm count. These mice may be suitable for use in studies related to estrogen signaling, estrous cycle, obesity, metabolic syndrome and hormonal regulation of a variety of organ systems.
Please note: Mice carrying this Esr1tm1Ksk allele (Stock No. 004744), express a low level of a truncated form of ERα, the result of alternate splicing of the transcript. In contrast, mice carrying the Esr1tm4.2Ksk allele (Stock No. 026176) have no tissue responses to estrogen and no estrogen receptor alpha activity.
Kenneth Korach, LRDT, NIEHS, NIH
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Esr1 | estrogen receptor 1 (alpha) |
The targeted Esr1 gene encodes a ligand-activated transcription factor and nuclear estradiol hormone receptor. In the ERKO line (Stock #004744) multiple transcript variants may form due to alternative cryptic splicing of the endogenous mouse Esr1 gene. These mice carry an insertional disruption mutation of the Esr1 gene in which exon 2 has been deleted and a series of stop codons have been inserted. Two truncated mutant transcripts and a truncated protein (approximately 61kDa in size) having a deleted N-terminus are detected in uterine tissue from homozygous female mice by RT-PCR and Western blot analysis.
At birth, mice homozygous for the targeted allele are viable and normal in size and appearance. Female homozygous mice are infertile, exhibit cystic ovaries that lack corpora lutea and have hypoplastic uteri that are unresponsive to estrogen. Homozygous males are infertile, low normal testis weight as adults and diminished sperm count (10% of normal.
Homozygous females have more than 4-fold higher level of serum estradiol and elevated androgen levels compared to wildtype controls, indicative of estrogen insensitivity. There is approximately 3% of the Estradiol binding in uterine tissue from homozygotes compared to levels observed in wildtype controls; no estradiol binding is detected in other tissues (brain, kidney, and liver) from homozygotes. Female neuroendocrine estrogen negative feedback is disrupted with highly elevated LH, normal FSH levels but no prolactin.
Please note: Mice carrying this Esr1tm1Ksk allele (Stock No. 004744), express a low level of a truncated form of ERα, the result of alternate splicing of the transcript. In contrast, mice carrying the Esr1tm4.2Ksk allele (Stock No. 026176) have no tissue responses to estrogen and no estrogen receptor alpha activity.
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter, and polyA signal sequence, was used to disrupt the second exon of the targeted gene. A herpes simplex virus thymidine kinase was used for negative selection. The construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Correctly targeted ES cells were injected into C57BL/6J blastocysts to obtain chimeric animals. This strain originated on a B6;129P2 background and has been backcrossed to C57BL/6 for ten generations.
Allele Name | targeted mutation 1, Kenneth S Korach |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | AERKO; alphaERKO; alpha-ERKO; ER1KO; ERalpha-; ER-alpha-; ERalphaKO; ERalpha-KO; ERalphaKOCH; ERa-Neo; ERKO; Esr1tm1Unc; Esr1tm1Ksk |
Gene Symbol and Name | Esr1, estrogen receptor 1 (alpha) |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 10 |
Molecular Note | Insertion of a PGK-neomycin resistance cassette into exon 2 disrupted the reading frame downstream of the ATG start site. ELISA studies using antibodies to the carboxy terminus detected low concentrations of endogenous protein in uterine tissue from homozygous mutant mice. RT-PCR analysis detected two truncated mutant transcripts in uterine tissue from homozygous mice. Western blot analysis detected a 61 kDa protein in uterine tissue from homozygotes. Transient transfection assays confirmed that this protein retains some transactivation activity in the presence of estradiol. |
Mutations Made By | Kenneth Korach, LRDT, NIEHS, NIH |
When maintaining a live colony, heterozygous mice may be bred to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). Homozygous females are infertile. The fertility of homozygous males is greatly reduced, but not abolished. The expected coat color is black.
When using the ERα KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004744 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or Wild-type for Esr1<tm1Ksk> |
Frozen Mouse Embryo | B6.129P2-Esr1<tm1Ksk>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129P2-Esr1<tm1Ksk>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129P2-Esr1<tm1Ksk>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6.129P2-Esr1<tm1Ksk>/J Frozen Embryos | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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