Widespread expression of the Dkk1 in this Hprt (hypoxanthine guanine phosphoribosyl transferase) mutant strain is regulated by a tetracycline operator (tetO), and activation of the Wnt signaling pathway can be monitored via the TOPGAL transgene. This strain may be useful in studies of the Wnt signaling pathway.
Stijn P. De Langhe, National Jewish Health
Genetic Background | Generation |
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Allele Type |
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Transgenic (Reporter) |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Transactivator) | Gt(ROSA)26Sor | gene trap ROSA 26, Philippe Soriano |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Inducible, Inserted expressed sequence) | Hprt | hypoxanthine guanine phosphoribosyl transferase |
The Dkk1 gene encodes for Dickkopf1, which is a canonical Wnt/Beta-catenin inhibitor. These mice carry a knock in allele containing the Dkk1 gene under the control of the tetO, tetracycline-responsive regulatory element, inserted into the endogenous Hprt locus on the X chromosome; the widespread expressing Gt(ROSA)26Sortm1.1(rtTA,EGFP)Nagy allele and the TOPGAL, Tg(TCF/Lef1-lacZ)34Efu transgene. Widespread expression of the the Dkk1 gene in all tissues is inducible with Doxycycline. The TOPGAL transgene acts as a Beta-galactosidase reporter for Wnt/Beta-catenin signaling activation. Females heterozygous/males hemizygous for the Hprttm1(tetO-Dkk1)Spdl (which is X-linked), homozygous for the Gt(ROSA)26Sortm1.1(rtTA,EGFP)Nagy allele and hemizygous for the Tg(TCF/Lef1-lacZ)34Efu transgene are viable and fertile.
A targeting vector containing the Tet-Dkk1 cassette (Dkk1 gene under the control of the tetO, tetracycline-responsive regulatory element) was inserted into the endogenous Hprt locus on the X chromosome. The construct was electroporated into mixed C57BL/6 and 129 derived BPES embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline The mice were crossed to Swiss Webster mice and several other mutant lines. The mice were crossed with TOPGAL mice carrying the Tg(TCF/Lef1-lacZ)34Efu transgene, as well as mice carrying the Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy allele. The mice were then crossed to CMV-cre mice expressing Cre recombinase in all tissues (Stock No. 003475) to remove the floxed STOP cassette in the Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy allele, resulting in the generation of the Gt(ROSA)26Sortm1.1(rtTA,EGFP)Nagy allele. The mice were crossed to Swiss Webster mice and no longer carry the Tg(CMV-cre)1Cgn transgene. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony and breed out any other mutant alleles.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression | lacZ expression occurs during early embryonic development in a subset of pluripotent embryonic basel cells of the epithelium and dermis of developing hair follicles. lacZ expression disappears during formation of hair germ and then reappears at E16.5 in hair follicles until 18 days after birth. |
Expressed Gene | GFP, Green Fluorescent Protein, |
Site of Expression | Widespread reverse tetracycline transactivator (rtTA)-expression. |
Expressed Gene | Dkk1, dickkopf WNT signaling pathway inhibitor 1, mouse, laboratory |
Site of Expression | Expression of Dkk1 is widespread under the control of tetO. |
Allele Name | transgene insertion 34, Elaine Fuchs |
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Allele Type | Transgenic (Reporter) |
Allele Synonym(s) | TCF-betagal; Tg(Fos-lacZ)34Efu; TOPGAL; Top-Gal |
Gene Symbol and Name | Tg(TCF/Lef1-lacZ)34Efu, transgene insertion 34, Elaine Fuchs |
Gene Synonym(s) | |
Promoter | Fos, Fos proto-oncogene, AP-1 transcription factor subunit, rat |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Site of Expression | lacZ expression occurs during early embryonic development in a subset of pluripotent embryonic basel cells of the epithelium and dermis of developing hair follicles. lacZ expression disappears during formation of hair germ and then reappears at E16.5 in hair follicles until 18 days after birth. |
Strain of Origin | Not Specified |
Chromosome | UN |
General Note | Homozygous transgenic mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Transgenic mice express beta-galactosidase in the presence of the lymphoid enhancer binding factor 1/transcription factor 3 (LEF1/TCF3) mediated signaling pathway and activated Beta-catenin (CATNB). Transgenic mice display Beta-galactosidase activity during early embryonic development in a subset of pluripotent embryonic basal cells of the epithelium and dermis of developing hair follicles. Beta-galactosidase activity is not detected in the next stage of hair follicle development, formation of hair germs. At E16.5, transgene activity reappears in hair follicles and is detectable until 18 days after birth. |
Molecular Note | The transgene contains the lacZ gene under the control of a promoter consisting of three consensus lymphoid enhancer binding factor 1/transcription factor 3 (LEF/TCF)-binding motifs upstream of a minimal Fos promoter. This allele is responsive to canonical Wnt/beta-catenin signal transduction. |
Mutations Made By | Elaine Fuchs, The Rockefeller University |
Allele Name | targeted mutation 1.1, Andras Nagy |
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Allele Type | Targeted (Reporter, Transactivator) |
Allele Synonym(s) | ROSA26rtTA |
Gene Symbol and Name | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano |
Gene Synonym(s) | |
Expressed Gene | GFP, Green Fluorescent Protein, |
Site of Expression | Widespread reverse tetracycline transactivator (rtTA)-expression. |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 6 |
Molecular Note | A targeting vector containing a floxed Pgk-neo-pA cassette and a rtTA-IRES-EGFP-pA cassette was inserted into intron 1 of the locus. Cre-mediated recombination removed the floxed neo cassette allowing the ROSA26 promoter to drive expression of rtTA and EGFP. Presence of doxycycline results in the formation of an active transcriptional activator and the activation of the responder transgene. |
Allele Name | targeted mutation 1, Stijn De Langhe |
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Allele Type | Targeted (Inducible, Inserted expressed sequence) |
Allele Synonym(s) | Tet-Dkk1 |
Gene Symbol and Name | Hprt, hypoxanthine guanine phosphoribosyl transferase |
Gene Synonym(s) | |
Promoter | tetO, tet operator, |
Expressed Gene | Dkk1, dickkopf WNT signaling pathway inhibitor 1, mouse, laboratory |
Site of Expression | Expression of Dkk1 is widespread under the control of tetO. |
Strain of Origin | (129-Hprtb-m3 x C57BL/6)F1 |
Chromosome | X |
Molecular Note | A targeting vector containing the tetracycline responsive promoter driving inducible expression of Dkk1 was inserted into the endogenous Hprt locus on the X chromosome. |
When maintaining a live colony, these mice can be bred as heterozygous/carrier females and hemizygous males for the Hprttm1(tetO-Dkk1)Spdl (which is X-linked), homozygous for the Gt(ROSA)26Sortm1.1(rtTA,EGFP)Nagy allele and hemizygous for the Tg(TCF/Lef1-lacZ)34Efu transgene.
Homozygous for Gt(ROSA)26Sortm1.1(rtTA,EGFP)Nagy, wildtype for Hprttm1(tetO-Dkk1)Spdl, Homozygous for Tg(TCF/Lef1-lacZ)34Efu x Homozygous for Gt(ROSA)26Sortm1.1(rtTA,EGFP)Nagy, Hemizygous for Hprttm1(tetO-Dkk1)Spdl, Homozygous for Tg(TCF/Lef1-lacZ)34Ef
When using the STOCK Gt(ROSA)26Sortm1.1(rtTA,EGFP)Nagy Hprttm1(tetO-Dkk1)Spdl Tg(TCF/Lef1-lacZ)34Efu/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024746 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous for Gt(ROSA)26Sor<tm1.1(rtTA,EGFP)Nagy>, Heterozyogus or wildtype for Hprt<tm1(tetO-Dkk1)Spdl> , Hemizygous or non carrier for Tg(TCF/Lef1-lacZ)34Efu |
Frozen Mouse Embryo | STOCK Gt(ROSA)26Sor<tm1.1(rtTA EGFP)Nagy> Hprt<tm1(tetO-Dkk1 | $2595.00 |
Frozen Mouse Embryo | STOCK Gt(ROSA)26Sor<tm1.1(rtTA EGFP)Nagy> Hprt<tm1(tetO-Dkk1 | $2595.00 |
Frozen Mouse Embryo | STOCK Gt(ROSA)26Sor<tm1.1(rtTA EGFP)Nagy> Hprt<tm1(tetO-Dkk1 | $3373.50 |
Frozen Mouse Embryo | STOCK Gt(ROSA)26Sor<tm1.1(rtTA EGFP)Nagy> Hprt<tm1(tetO-Dkk1 | $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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