Overview

Also Known As:Lrig1-CreERT2

This strain is currently unavailable due to replenishing of cryopreserved stocks. Interested customers who register interest will be contacted when the strain is again available.

In this strain Cre-ERT2 is knocked into the translational start site of the Lrig1 (leucine-rich repeats and immunoglobulin-like domains 1) gene. This strain may be useful for mediating inducible cre recombination in Lrig1 expressing tissues, and for applications in lineage mapping proliferative and quiescent intestinal progenitor cells.

Donating Investigator

Dr. Robert J. Coffey, Vanderbilt University Medical Center

Genetic overview

Genetic Background	Generation

Lrig1^{tm1.1(cre/ERT2)Rjc}

Allele Type	Gene Symbol	Gene Name
Targeted (Recombinase-expressing, Inducible)	Lrig1	leucine-rich repeats and immunoglobulin-like domains 1

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Research Applications

Cancer Research
Research Tools

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Details

Detailed Description

Lrig1 (leucine-rich repeats and immunoglobulin-like domains 1) encodes a transmembrane protein that negatively regulates ErbB receptors, Met and Ret, and is a marker for intestinal and skin progenitor cells. These Lrig1-CreERT2 mice carry a targeted mutation in which Cre-ERT2 is knocked into the endogenous ATG site of the Lrig1 gene. Although homozygotes are viable and fertile on the mixed B6;129 background, by 6 months of age homozygotes develop duodenal adenomas and some homozygous females exhibit impaired lactation. Homozygotes on the congenic C57BL/6 background exhibit an embryonic lethal phenotype. Heterozygotes are viable and fertile. These mice display robust inducible Cre recombination activity at a greater efficiency than that seen in Lgr5-EGFP-IRES-CreERT2 mice (Stock No. 008875). The Cre-ERT2 fusion protein is only active when it binds to the estrogen analog 4-hydroxytamoxifen (OHT). When these mice are bred with mice containing a loxP-flanked sequence, tamoxifen-inducible Cre-mediated recombination is expected to result in deletion of the floxed sequences in the Cre recombinase and Lrig1 expressing quiescent intestinal, gastric epithelium and skin progenitor cells of the offspring.

Development

A targeting vector designed by Dr. Robert J. Coffey (Vanderbilt University) containing sequence encoding Cre recombinase-estrogen receptor (Cre-ERT2) fusion protein, SV40 polyA signal, and an FRT-flanked PGK-neo cassette was inserted immediately after the endogenous ATG site of Lrig1. The construct was electroporated into 129S6/SvEvTac derived TL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to B6.Cg-Tg(ACTFLPe)9205Dym/J (Stock No. 005703) mice to remove the FRT site flanked NEO cassette. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Expression Data

Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	Intestinal colonic stem cells located at the crypt base.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Powell AE; Wang Y; Li Y; Poulin EJ; Means AL; Washington MK; Higginbotham JN; Juchheim A; Prasad N; Levy SE; Guo Y; Shyr Y; Aronow BJ; Haigis KM; Franklin JL; Coffey RJ. 2012. The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell 149(1):146-58PubMed: 22464327 MGI: J:186084

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Genetics

Lrig1^{tm1.1(cre/ERT2)Rjc}

Allele Symbol: Lrig1^{tm1.1(cre/ERT2)Rjc}

Allele Name	targeted mutation 1.1, Robert J Coffey
Allele Type	Targeted (Recombinase-expressing, Inducible)
Allele Synonym(s)	Lrig1-CreERT2
Gene Symbol and Name	Lrig1, leucine-rich repeats and immunoglobulin-like domains 1
Gene Synonym(s)
Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	Intestinal colonic stem cells located at the crypt base.
Strain of Origin	129S6/SvEvTac
Chromosome	6
Molecular Note	The targeting vector used for homologous recombination was generated by BAC recombineering. A tamoxifen-inducible cre (cre/ERT2) sequence, SV40 polyA signal, and an Frt-flanked PGK-neo cassette were targeted to the endogenous ATG site of Lrig1. Chimeras were crossed with Flpe-expressing animals to remove the neo from the germline.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cancer Research
- Increased Tumor Incidence
  - Adenomas: intestinal adenomas
Research Tools
- Cre-lox System
  - Cre Recombinase Expression: Inducible
  - Tamoxifen-inducible

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Lrig1^{tm1.1(cre/ERT2)Rjc}/Lrig1^{tm1.1(cre/ERT2)Rjc}
involves: 129 * C57BL/6

normal phenotype

no abnormal phenotype detected
- homozygotes (and heterozygotes) are viable and fertile

References

Powell AE; Wang Y; Li Y; Poulin EJ; Means AL; Washington MK; Higginbotham JN; Juchheim A; Prasad N; Levy SE; Guo Y; Shyr Y; Aronow BJ; Haigis KM; Franklin JL; Coffey RJ. 2012. The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell 149(1):146-58PubMed: 22464327 MGI: J:186084

Additional - Lrig1^{tm1.1(cre/ERT2)Rjc} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Probe:Generic Cre Probe
- Separated PCR:Lrig1alternate3
- Standard PCR:Generic Cre Melt Curve Analysis
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes on the congenic C57BL/6 background are not viable.
- Additional Breeding and Husbandry Support
Citation
When using the Lrig1-CreERT2 mouse strain in a publication, please cite the originating article(s) and include JAX stock #018418 in your Materials and Methods section.

Strain Interest Registration

Please fill out the form below to indicate your interest in purchasing this JAX®Mice strain.
This information helps us manage the colony build and better meet the broad needs of the research community.
Please send any technical questions to Technical Support.

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Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Lrig1-CreERT2

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Lrig1tm1.1(cre/ERT2)Rjc

Allele Symbol: Lrig1tm1.1(cre/ERT2)Rjc

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Lrig1tm1.1(cre/ERT2)Rjc/Lrig1tm1.1(cre/ERT2)Rjcinvolves: 129 * C57BL/6

normal phenotype

References

Additional - Lrig1tm1.1(cre/ERT2)Rjc related

Genotyping Protocols

Breeding Considerations

Citation

Strain Interest Registration

Contact Information

Interest

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Lrig1^{tm1.1(cre/ERT2)Rjc}

Allele Symbol: Lrig1^{tm1.1(cre/ERT2)Rjc}

Genotype: Lrig1^{tm1.1(cre/ERT2)Rjc}/Lrig1^{tm1.1(cre/ERT2)Rjc}
involves: 129 * C57BL/6

Additional - Lrig1^{tm1.1(cre/ERT2)Rjc} related