These Esr1 knock-out mice exhibit infertility. Female homozygotes display elevated serum levels of testosterone, estradiol, and luteinizing hormone. They are suitable for use in applications related to the study of the estrogen hormone signalling pathway.
Kenneth Korach, LRDT, NIEHS, NIH
Estrogen receptor 1 is one of 2 estrogen receptors, a ligand-activated transcription factor and nuclear hormone receptor. These mice carry a knock out mutation of the Esr1 gene in which exon 3 has been deleted. Homozygotes are viable but not fertile. No gene product (protein) is detected by Western blot analysis of uterine tissue. A faint band of truncated gene product (transcript), consistent with the deletion of exon 3, is detected by RT-PCR of uterine RNA. Tissue response to estrogen and estrogen receptor alpha activity is eliminated in homozygotes.
Homozygous females exhibit increased elevated serum testosterone, estradiol, and
luteinizing hormone levels, as well as impaired mammary gland development and uterine proliferation. Male and female growth curves are similar and do not show the sexual dimorphism in growth observed in wildtype controls. Female homozygotes have increased body weights, total body fat, and bone mineral density than wildtype female mice.
A targeting vector containing floxed TK-neo selection cassette was inserted downstream of exon 3 and a third loxP site was inserted upstream of exon 3. The construct was electroporated into unspecified C57BL/6NTac derived embryonic stem (ES) cell line. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were crossed with mice on an unknown background and carrying the Tg(Sox2-cre)1Amc transgene to remove the floxed TK-neo cassette. The mice were the backcrossed to C57BL/6NCrl using a marker assisted protocol (see SNP note below). Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6NJ (Stock No. 005304) at least once to establish the colony.
In 2019, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One of the 5 markers that determine C57BL/6J from C57BL/6N, the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus, was found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.
|Allele Name||targeted mutation 4.2, Kenneth S Korach|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Ex3alphaERKO; Ex3-ERKO|
|Gene Symbol and Name||Esr1, estrogen receptor 1 (alpha)|
|Strain of Origin||C57BL/6NTac|
|Molecular Note||A floxed TK-neo selection cassette was inserted downstream of exon 3 and a third loxP site was inserted upstream. The selection cassette and exon 3 were subsequently removed from properly targeted mice by cre excision.|
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6NJ inbred mice (Stock No. 005304). Homozygotes are viable but not fertile.
When using the B6N(Cg)-Esr1tm4.2Ksk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #026176 in your Materials and Methods section.