FVB.B6-Esr1^tm4.1Ksk/DpmJ

Stock number: 038948
Product name: FVB-ERα^lox
Strain synonyms: FVB-loxERa
Research areas: Cancer Research, Developmental Biology Research, Internal/Organ Research, Research Tools

Description

FVB-ERα^lox mice possess loxP sites flanking exon 3 of the estrogen receptor 1 (alpha) (Esr1) gene. This strain may be useful for studying the role of estrogen receptors in the regulation of mammary epithelial cell proliferation and differentiation during development and during pregnancy.

Stock No. 038948 is an FVB/N-congenic ERα^lox floxed mouse line. Of note, the same ERα^lox floxed allele is also available on a C57BL/6-background as Stock No. 032173.

Detailed description

These FVB-ERα^lox mice possess loxP sites flanking exon 3 of the estrogen receptor 1 (alpha) (Esr1) gene. ESR1 encodes a nuclear hormone receptor that is predominantly expressed in the uterus, mammary glands, pituitary, hypothalamus, and ovarian theca cells and is important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2 (ESR2). Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Exon 3 is required for DNA binding. Mice that are homozygous for this allele are viable. Note that the donating laboratory indicates that when crossing these ERα^lox mice to a Cre-recombinase line, they did not use the ERα^lox;Cre+ females for breeding to avoid any issues with fertility and/or lactation due to loss of Esr1 in the female germline. When crossing to a Cre-recombinase line, the suggested breeding scheme is to utilize ERα^lox females crossed to Cre+ males only. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in cre-expressing tissues.

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. It should be noted that the phenotype of these FVB/N-congenic mice could vary from that originally described on a C57BL/6 background. We may modify the strain description if necessary, as published results become available.

Development

The ERα^lox targeting vector was designed by Dr. Kenneth Korach, to insert a loxP-flanked neomycin resistance (neo) cassette downstream of exon 3, and a single loxP site upstream of exon 3 of the estrogen receptor 1 (alpha) (Esr1) gene. The construct was electroporated into C57BL/6NTac-derived embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre expression plasmid to delete the neo cassette. Resulting ES cells contained multiple gene rearrangements; intact floxed-exon 3, intact floxed-neo cassette, or excision of both exon 3 and the neo cassette. Correctly targeted ES cells, containing only the floxed-exon 3 mutation, were injected into B6 albino blastocysts. Resulting chimeric males were bred with C57BL/6NCrl mice for 2 generations prior to arriving at The Jackson Laboratory as Stock No. 032173.

Dr. Donald McDonnell received some ERα^lox mice, on a C57BL/6 background, from Dr. Kenneth Korach (similar to JAX Stock No. 032173) and backcrossed these mice to FVB/NJ inbred mice for at least five generations. The resulting FVB-congenic ERα^lox mice, with floxed exon 3 intact, is called FVB.Cg-Esr1^tm4.1Ksk/DpmJ (Stock No 038948). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ (Stock No. 001800) oocytes.

In 2024, 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 males sent to The Jackson Laboratory Repository. Two of the 43 markers throughout the genome were segregating with C57BL/6J on Chromosomes 2 and 14.

Allele

Symbol: Esr1^tm4.1Ksk
Name: targeted mutation 1.1, Kenneth S Korach
MGI accession ID: MGI:5465423
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
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
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 was subsequently removed from properly targeted mice by cre excision leaving exon 3 flanked by loxP sites.