C57BL/6-Esr1^{tm2.1(cre)And}/J

Stock number: 017913
Product name: Esr1-Cre
Research areas: Cancer Research, Cell Biology Research, Endocrine Deficiency Research, Neurobiology Research, Reproductive Biology Research, Research Tools

Description

The Esr1^cre knockin allele has Cre recombinase expression directed to estrogen receptor 1 alpha (Esr1 or ERα)-expressing cells by the endogenous Esr1 promoter/enhancer elements; specifically in the ventrolateral subdivision of the ventromedial hypothalamus that, like wildtype mice, is greater in females than males. Expression is also observed in arcuate nucleus (ARH). These Esr1-Cre knockin mice may be useful for studying the function of this ligand-inducible transcription factor in social interactions, neuronal differentiation, sympathetic nervous system development, hypothalamus, female reproductive organs (endometrium and ovarian stroma cells), and male efferent duct epithelial cells. They may also be useful for studying ERα-positive breast cancer and steroid hormone-induced malignancies. Esr1-Cre knockin mice are available on a C57BL/6N background (Stock No. 017911) and a C57BL/6J background (Stock No. 017913).

Detailed description

The Esr1^cre (Esr1-Cre) knockin allele harbors an attP-flanked 2A oligopeptide and Cre recombinase gene in the 3' UTR of the estrogen receptor 1 alpha gene (Esr1 or ERα). Under direction of the endogenous Esr1 promoter/enhancer elements, Cre recombinase expression is observed in a pattern similar to that of Esr1. The donating investigator specifically reports Cre recombinase expression in the ventrolateral subdivision of the ventromedial hypothalamus (VMHv1) that, like wildtype mice, is greater in females than males. Expression is also observed in arcuate nucleus (ARH). The donating investigator reports that heterozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

The phenotype of C57BL/6NJ-congenic Esr1-Cre knockin mice (Stock No. 017911) is described above. In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the C57BL/6J-congenic Esr1-Cre knockin strain (Stock No. 017913). It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

In 2014, it is the experience of The Jackson Laboratory Repository colony managers that C57BL/6J-congenic Esr1-Cre knockin homozygotes of both sexes are viable and fertile with no breeding deficiencies.

ERα, a nuclear hormone receptor (NHR), binds to steroid hormones in the cytoplasm, causing their translocation into the nucleus and leading to increased transcription of target genes. These Esr1-Cre knockin mice may be useful for studying the function of this ligand-inducible transcription factor in neuronal differentiation, sympathetic nervous system development, hypothalamus, female reproductive organs (endometrium and ovarian stroma cells), and male efferent duct epithelial cells. They may also be useful for studying ERα-positive breast cancer and steroid hormone-induced malignancies.

Development

The Esr1^cre (Esr1-Cre) knockin allele was designed by Dr. David J. Anderson (California Institute of Technology) to insert an attP site, a 2A oligopeptide (mediates ribosomal skipping), the Cre recombinase gene, a frt-flanked PGKneo-polyA cassette, and an attP site within the 3' UTR of the estrogen receptor 1 alpha gene (Esr1). The targeting construct was electroporated into C57BL/6N-derived PRX-B6N embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Chimeric males were bred with C57BL/6 females (Taconic) to establish the colony. The resulting offspring were bred to CAG-FLPe transgenic mice (coisogenic on the C57BL/6J genetic background) to remove the frt-flanked PGKneo-polyA cassette. Heterozygous Esr1-Cre knockin mice were backcrossed to C57BL/6J mice (from The Jackson Laboratory) for one more generation prior to sending black mutant mice to The Jackson Laboratory Repository in 2012. Upon arrival at The Jackson Laboratory Repository, Esr1-Cre mice were bred to C57BL/6J inbred mice (Stock No. 000664) for seven generations using a marker-assisted speed congenic approach. As of January 2014, the C57BL/6J-congenic Esr1^cre knockin colony has all markers that determine C57BL/6 substrains confirmed to be C57BL/6J allele-type. Overall, all 149 markers are C57BL/6 allele-type.

Allele

Symbol: Esr1^{tm2.1(cre)And}
Name: targeted mutation 2.1, David J Anderson
MGI accession ID: MGI:5605085
Generation method: Targeted
Attributes: Recombinase-expressing; RMCE-ready
Marker symbol: Esr1
Marker name: estrogen receptor 1 (alpha)
Marker synonyms: ER; ER[a]; Era; ERalpha; ER-alpha; Esr; ESRA; Estr; Estra; ESTRR; NR3A1; RNESTROR
Chromosome: 10
Strain of origin: C57BL/6NTac
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: Cre recombinase is expressed in the ventrolateral subdivision of the ventromedial hypothalamus, but greater in females than males. Expression is also observed in arcuate nucleus.
Molecular note: The targeting vector was designed to insert an attP site, a 2A oligopeptide (mediates ribosomal skipping), the Cre recombinase gene, a FRT-flanked PGKneo-polyA cassette, and an attP site within the 3' UTR of the gene. Flpe-mediated recombination removed the neo cassette.