B6N.129S6(Cg)-Esr1^{tm1.1(cre)And}/J

Stock number: 017911
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. In 2014, it is the experience of The Jackson Laboratory Repository colony managers that C57BL/6NJ-congenic Esr1-Cre knockin homozygotes of both sexes do not breed well.

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 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with 129S6/SvEvTac females to establish the colony. Heterozygous mice were backcrossed to C57BL/6N for two generations. Next, a heterozygous male was bred to ACT-FLPe mice (backcrossed onto C57BL/6 background) to remove the frt-flanked PGKneo-polyA cassette. The resulting Esr1-Cre knockin mice were bred to C57BL/6N mice for one more generation (and the ACT-FLPe transgene removed) prior to sending black mutant mice to The Jackson Laboratory Repository in 2012. Upon arrival at The Jackson Laboratory Repository, mutant mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for several generations using a marker-assisted speed congenic approach. As of April 2014, the C57BL/6NJ-congenic Esr1^cre knockin colony has all markers that determine C57BL/6 substrains confirmed to be C57BL/6N allele-type. Overall, at least 148/149 markers (99%) are C57BL/6 allele-type. The single segregating marker is 129 allele-type on chromosome 10 near the targeted locus (consistent with contributions from the ES cell used in creating the targeted mutation).

Allele

Symbol: Esr1^{tm1.1(cre)And}
Name: targeted mutation 1.1, David J Anderson
MGI accession ID: MGI:5559339
Generation method: Targeted
Attributes: Recombinase-expressing; RMCE-ready
Synonyms: Esr1^cre; Esr1cre
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: 129S6/SvEvTac
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: Cre recombinase is expressed in the ventrolateral subdivision of the ventromedial hypothalamus, and also in the arcuate nucleus.
Molecular note: The Esr1-cre 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 estrogen receptor 1 alpha gene (Esr1). The targeting construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Chimeric males were bred with 129S6/SvEvTac females to establish the colony. Heterozygotes were bred to ACT-FLPe mice to remove the frt-flanked PGKneo-polyA cassette. Mice were bred to remove the ACT-FLPe transgene from the background.