The Foxd1GCE allele expresses an eGFPCreERT2 fusion protein (EGFP and creERT2 fusion protein) from the Foxd1 promoter/enhancer elements. These mice may be useful for studying therapeutic strategies directly targeting pericyte differentiation in vivo and may productively impact fibrotic kidney disease.
Andrew P McMahon, University of Southern California
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Recombinase-expressing, Reporter, Inducible) | Foxd1 | forkhead box D1 |
Heterozygous mice are viable and fertile, normal in size and do not display any gross physical or behavioral abnormalities. The DI states that the strain is homozygous lethal. The Foxd1GCE allele expresses an eGFPCreERT2 fusion protein (EGFP and creERT2 fusion protein) from the Foxd1 promoter/enhancer elements. Foxd1 is induced, and EGFP immunofluorescence is observed, during kidney development in metanephric mesenchyme in cells fated to become stromal cells of the kidney. Cre-ERT2 fusion gene activity is inducible; observed in the same cells only following tamoxifen administration. When Foxd1GCE mice are bred with mice containing loxP-flanked sequence, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the floxed sequences in the FoxD1-expressing cells of the offspring. These mice may be useful for studying therapeutic strategies directly targeting pericyte differentiation in vivo and may productively impact fibrotic kidney disease.
The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17β-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.
A targeting vector was designed to insert an eGFPCreERT2 (GCE) fusion protein coding sequence and frt-flanked PGKneobpA selection cassette into the initiation codon of the Forkhead box D1 (Foxd1) targeted gene. Specifically, this targeting vector contained an enhanced green fluorescent protein (EGFP) and a CreERT2 fusion gene (Cre-ERT2; Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain). This construct was electroporated into F1 hybrid (C57BL/6 x 129S4Sv/Jae)-derived v6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6J females. These FoxD1-GCE (Foxd1GCE) mutant mice were maintained on this mixed C57BL/6J;129/Sv genetic background. Upon arrival at The Jackson Laboratory, mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | GFP, Green Fluorescent Protein, |
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Expressed Gene | cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene, |
Site of Expression | Foxd1 is induced, and EGFP immunofluorescence is observed, during kidney development in metanephric mesenchyme in cells fated to become stromal cells of the kidney. |
Allele Name | targeted mutation 2, Andrew P McMahon |
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Allele Type | Targeted (Recombinase-expressing, Reporter, Inducible) |
Allele Synonym(s) | FoxD1-GCE |
Gene Symbol and Name | Foxd1, forkhead box D1 |
Gene Synonym(s) | |
Expressed Gene | GFP, Green Fluorescent Protein, |
Expressed Gene | cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene, |
Site of Expression | Foxd1 is induced, and EGFP immunofluorescence is observed, during kidney development in metanephric mesenchyme in cells fated to become stromal cells of the kidney. |
Strain of Origin | (C57BL/6 x 129S4/SvJae)F1 |
Chromosome | 13 |
Molecular Note | A targeting vector was designed to insert an eGFP/Cre/ERT2 (GCE) fusion protein coding sequence and frt-flanked PGKneobpA selection cassette into the initiation codon of the Forkhead box D1 (Foxd1) targeted gene. |
When maintaining a live colony, transgenic mice may be bred to wildtype (noncarrier) mice from the colony or with C57BL/6J inbred mice (Stock No. 000664). Homozygous mice are embryonic lethal.
When using the B6;129S4-Foxd1tm2(GFP/cre/ERT2)Amc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012464 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Foxd1<tm2(GFP/cre/ERT2)Amc> |
Frozen Mouse Embryo | B6;129S4-Foxd1<tm2(GFP/cre/ERT2)Amc>/J | $2595.00 |
Frozen Mouse Embryo | B6;129S4-Foxd1<tm2(GFP/cre/ERT2)Amc>/J | $2595.00 |
Frozen Mouse Embryo | B6;129S4-Foxd1<tm2(GFP/cre/ERT2)Amc>/J | $3373.50 |
Frozen Mouse Embryo | B6;129S4-Foxd1<tm2(GFP/cre/ERT2)Amc>/J | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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