STOCK Ager^{tm2.1(cre/ERT2)Blh}/2J

Stock number: 036942
Product name: Ager-CreER^T2
Research areas: Research Tools

Description

Ager-CreER^T2 mice carry a tamoxifen-inducible cre/ERT2 fusion gene inserted into the start codon of the advanced glycosylation end product-specific receptor (Ager) gene. Insertion of this fusion gene abolishes Ager gene expression.

Note: Reports have been received from investigators that mice acquired from the original importation of this strain (see Stock No. 032771) do not demonstrate inducible alveolar epithelial type I (AT1) cell-specific expression as described in the literature. These findings may be due to experimental variation and have not been confirmed at our facility. Further investigation is underway. As a precautionary measure we have re-imported animals (new Stock No. 036942) having a phenotype reported to be more consistent with the original findings. (November, 2021)

Detailed description

Ager-CreER^T2 mice carry a tamoxifen-inducible cre/ERT2 fusion gene inserted into the start codon of the advanced glycosylation end product-specific receptor (Ager) gene. Insertion of this fusion gene abolishes Ager gene expression.

Ager encodes a transmembrane receptor expressed at the highest levels in the lung compared to other tissues, in particular in alveolar epithelial type I (AT1) cells. It is involved in homeostasis, development, atherosclerosis, aging, and inflammation, and certain diseases, such as diabetes, and Alzheimer's disease. Mice that are homozygous for this knock-in/knock-out allele are viable and fertile.

When Ager-CreER^T2 mice are bred with mice containing loxP-flanked sequence(s), tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequence(s) in the Cre-expressing cells of the offspring. Cre recombination occurs in alveolar epithelial type I (AT1) cells.

Note: Reports have been received from investigators that mice acquired from the original importation of this strain (see Stock No. 032771) do not demonstrate inducible AT1 cell-specific expression as described in the literature. These findings may be due to experimental variation and have not been confirmed at our facility. Further investigation is underway. As a precautionary measure we have re-imported animals (new Stock No. 036942) having a phenotype reported to be more consistent with the original findings. (November, 2021)

Development

The Ager-CreER^T2 targeting vector was designed to insert a cre/ERT2 fusion gene (Cre recombinase fused to a human estrogen receptor ligand binding domain), followed by a polyadenylation signal and a frt-flanked neomycin resistance cassette, into the start codon of the advanced glycosylation end product-specific receptor (Ager) gene. The construct was electroporated into (129S6/SvEvTac x C57BL/6NCr)F1-derived G4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred with 129S4-Gt(ROSA)26Sor^tm2(FLP*)Sor/J mice (Stock No. 007844) to remove the neo cassette. Resulting Ager-CreER^T2 mice were bred to C57BL/6J mice for at least 15 generations by the donating laboratory (see SNP note below). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Note: This strain represents a re-importation of Stock No. 032771. More details may be found in the Detailed Description section.

In 2022, 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. Many of the 43 markers throughout the genome were segregating with 129, suggesting an incomplete backcross.

Allele

Symbol: Ager^{tm2.1(cre/ERT2)Blh}
Name: targeted mutation 2.1, Brigid L Hogan
MGI accession ID: MGI:6203633
Generation method: Targeted
Attributes: Recombinase-expressing; Inducible; Null/Knockout
Synonyms: Ager-CreER^T2
Marker symbol: Ager
Marker name: advanced glycosylation end product-specific receptor
Marker synonyms: RAGE; SCARJ1; sRAGE
Chromosome: 17
Strain of origin: (129S6/SvEvTac x C57BL/6NCrl)F1
Site of expression: Alveolar epithelial cells of the lung - see Stock Nos. 036942 / 032771.
Molecular note: The targeting vector was designed to insert a cre/ERT2 fusion gene, followed by a polyadenylation signal and a frt-flanked neomycin resistance cassette, into the start codon of Ager gene. The construct was electroporated into ES cells for homologous recombination. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred with FLP-deleter mice to remove the neo cassette. It is a null allele. Ager protein is not detected in lungs of the homozygous mice.