These EAAE mutant mice express a estrogen receptor 1 with a mutated DNA binding domain which results in loss-of-function. Homozygotes are infertile. They are suitable for use in applications related to the study of the estrogen hormone signalling pathway, specifically the role of a functional DNA binding domain in the physiological response to estrogens.
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 4 amino acid substitution mutations (Y201E, K210A, K214A, R215E) in the Esr1 gene, which are in the region encoding the DNA-binding domain, and a loss-of-function mutant estrogen receptor 1 results. Homozygotes are viable but not fertile. Heterozygotes are viable and fertile. Female homozygotes exhibit hypoplastic uterus, hemorrhagic ovaries, impaired ductal mammary gland development, which are phenotypic traits similar to those seen in Esr1 knock out mice. Male homozygotes are also infertile and exhibit a reproductive abnormalities phenotype similar to that observed in Esr1 knock out mice. Gene product (protein) is detected by immunoblot analysis of liver nuclear extracts and uterine samples from homozygotes.
A targeting vector containing a floxed NEO cassette was used to introduce 4 amino acid substitution mutations (Y201E, K210A, K214A, R215E) into the Esr1 locus. The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. ES cells that had successfully undergone Cre-mediated recombination and no longer retained the cassette were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 2.1, Gunther Schutz|
|Gene Symbol and Name||Esr1, estrogen receptor 1 (alpha)|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||Nucleotide substitutions resulted in amino acid substitutions of glutamic acid for tyrosine at position 201 (Y201E), alanine for lysine at position 210 (K210A), alanine for lysine at position 214 (K214A), and glutamic acid for arginine at position 215 (R215E). A floxed neo cassette used for selection was removed by transient cre expression in ES cells. The mutated amino acids are a part of the DNA recognition helix.|
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). Homozygotes are viable but not fertile.
When using the B6;129P2-Esr1tm2.1Gsc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #026178 in your Materials and Methods section.