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Genes & Alleles

Gli1;   Gli1tm3(cre/ESR1)Alj;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Targeted Mutation Species laboratory mouse Donating Investigator Alexandra Joyner,   Sloan-Kettering Institute

Strain Description
Mice homozygous for this Gli1-CreER^T2 targeted allele are viable and fertile (although homozygous males are reported to have breeding problems). Under control of the endogenous upstream promoter/enhancer elements, tamoxifen-inducible cre activity is observed in cells that have received positive Hedgehog/Sonic Hedgehog signaling. 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 (17b-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen 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. When these Gli1-CreER^T2 mice are bred with mice containing a loxP-flanked sequence of interest, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the flanked sequences in Gli1 expressing cells; making them useful for studying axis patterning, proliferation, and cell fate specification of Hedgehog responding cells at different stages of embryogenesis.

Strain Development
A targeting vector was designed with a CreERT2 fusion gene (Cre-ER^T2; Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain) followed by three tandem SV40 polyA sequence repeats and a reverse-oriented loxP-flanked neo cassette. This construct was inserted into the targeted gene (replacing a 2.3 kb region including the ATG site in exon 2 and first zinc finger domain in exon 4) via electroporation into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric mice were bred to either Black-Swiss or C57BL/6J mice. The Gli1-CreER^T2-neo heterozygotes were then bred to cre expressing mice (Black-Swiss genetic background) to remove the neo cassette. The resulting Gli1-CreER^T2 offspring (with a single loxP site remaining after the SV40 polyA sequences) were bred to Swiss Webster outbred mice for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J mice for at least one generation to establish the colony.

Mammalian Phenotype Terms assigned by genotype Gli1tm3(cre/ESR1)Alj/Gli1tm3(cre/ESR1)Alj         involves: 129S6/SvEvTac * Black Swiss no phenotypic analysis *normal* no phenotypic analysis (MGI Ref ID J:92507) knock-in mice with a tamoxifen inducible cre insert were designed to follow cell lines derived from progenitors that responded to Shh signalling

Gene & Allele Details

Allele Symbol		Gli1tm3(cre/ESR1)Alj
Allele Name		targeted mutation 3, Alexandra L Joyner
Common Name(s)		Gli1-CreERT2; Gli1tm3(cre/ERT2)Alj;
Mutation Made By		Alexandra Joyner,   Sloan-Kettering Institute
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		W4
ES Cell Line Strain		129S6/SvEvTac
Site of Expression		tamoxifen-inducible cre activity is observed in cells that have received positive Hedgehog/Sonic Hedgehog signaling
Gene Symbol and Name		Gli1, GLI-Kruppel family member GLI1
Chromosome		10
Gene Common Name(s)		AV235269; GLI; Zfp-5; Zfp5; expressed sequence AV235269; zinc finger protein 5;
Molecular Note		CreERT2 cDNA and a floxed neo were inserted into the 5' UTR of the first coding exon. Crossing with mice expressing Cre removed the floxed neo. [MGI Ref ID J:92507]

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Genotyping Protocols

Gli1^{tm3(cre/ESR1)Alj}

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous mice mice may be bred. The donating investigator reports that homozygous males do not breed well.

Additional Web Information

Cre-lox or FLP-FRT Systems

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Cre-lox System (Cre Recombinase expression in neural tissue)

Research Tools
Cre-lox System (Cre-Recombinase Expression: Inducible)
Developmental Biology Research (Cre-lox System)
Genetics Research (Mutagenesis and Transgenesis: Cre-lox System)
Genetics Research (Tissue/Cell Markers: Cre-lox System)

References

Selected Reference(s)

Ahn S; Joyner AL. 2004. Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning. Cell 118(4):505-16. [PubMed: 15315762]  [MGI Ref ID J:92507]

Additional References

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Price and Supply Information

Strain Name:	STOCK Gli1tm3(cre/ESR1)Alj/J
Stock Number:	007913

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development

Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	This strain is included in the Induced Mutant Resource Colony collection.
Licensing	See General Terms and Conditions below for Licensing and Use Restrictions
Control Information	View Control Information in Strain Details.

General Terms and Conditions

View JAX^® Mice & Services Conditions of Use.

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Notice Regarding cre/Esr1 (Tamoxifen Inducible Cre) Strains.
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

The Jackson Laboratory's Genotype Promise

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.

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