Overview

Also Known As:Rorc(γt)-EGFP

These mice harbor the reporter Rorcγt^GFP mutant and may be useful in studying immune system homeostasis, T cell repertoire selection, CD4/CD8 double positive thymocyte survival, lymphoid organogenesis, proinflammatory T-helper cell development, mucosal immunology, and the role of inflammatory disease in autoimmunity and cancer progression.

Donating Investigator

Dr. Dan R. Littman, New York University Medical Center

Genetic overview

Genetic Background	Generation
	N6+N3F9 (2021-01-14 00:00:00)

Rorc^tm2Litt

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Rorc	RAR-related orphan receptor gamma

View Genetics

Research Applications

Research Tools
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Developmental Biology Research
Apoptosis Research
Cancer Research

View All Research Applications

Base Price

Starting at:

$255.00 Domestic price for female 4-week

510.00 Domestic price for breeder pair

View Price List

Details

Detailed Description

Mice homozygous for this Rorc(γt^GFP (or RORγt)^GFP) mutant allele are viable and fertile. While Rorcγ mRNA is detected in liver in Rorc(γ)t^GFP homozygotes, mRNA and protein for the thymus-specific isoform (Rorcγt) encoded by the targeted allele are not detected in the thymus. EGFP expression reports Rorc(γt) transcription in the thymi of adult Rorc(γt)GFP mice. Homozygous mice exhibit abnormal lymph node, Peyer's patch, and lymphoid tissue inducer (LTi) cell development. Mice with Rorcγt-deficient T cells lack tissue-infiltrating proinflammatory T-helper cells (Th17 cells), and are protected from induced autoimmune disease (EAE) on this genetic background.

The donating investigator also reports increased thymoma incidence in homozygotes, with 80-90% of homozygotes succumbing to thymomas by 12-14 weeks of age. It should be noted that the time to onset may vary due to vivarium-specific environmental factors. In the JAX Repository colony, we have observed that female homozygotes live to 9-11 weeks of age and most male homozygotes die before 8 months of age (October 2015). Some researchers observe a much earlier onset. These RorcγtGFP mutant mice may be useful in applications related to immune homeostasis, T cell repertoire selection, CD4/CD8 double positive (CD4⁺/CD8⁺) thymocyte survival, and the role of inflammatory disease in autoimmunity and cancer progression.

Development

A targeting vector was designed to insert the coding sequence of Enhanced Green Fluorescent Protein (EGFP), followed by a loxP-flanked neomycin resistance cassette, into "exon 1γt" directly downstream of the ATG translational start codon of the targeted gene. The construct was electroporated into the 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts, and chimeras were bred to unspecified mice to generate Rorc(γt)^GFPneo heterozygotes. These mice were then crossed with a Cre-deleter strain (unspecified genetic background) to excise the neo cassette. The donating investigator reported that the resulting Rorc(γt)^GFP pups were then backcrossed to C57BL/6 (see SNP note below) for at least five generations prior to arrival at The Jackson Laboratory.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, at least 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	EGFP expression is reported in the thymus (cortex) of adult mice. EGFP is expressed in double-positive thymocytes, with small amounts of EGFP in CD4⁺ and CD8⁺ single-positive thymocytes.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Eberl G; Marmon S; Sunshine MJ; Rennert PD; Choi Y; Littman DR. 2004. An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol 5(1):64-73PubMed: 14691482 MGI: J:87395
Ivanov II; McKenzie BS; Zhou L; Tadokoro CE; Lepelley A; Lafaille JJ; Cua DJ; Littman DR. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126(6):1121-33PubMed: 16990136 MGI: J:115922

View All References

Genetics

Rorc^tm2Litt

Allele Symbol: Rorc^tm2Litt

Allele Name	targeted mutation 2, Dan R Littman
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Roc(gt)^gfp; Rorc(gammat)^-; Rorc(gammat)-EGFP; Rorc^GFP; RORgammat; RORgammat-EGFP
Gene Symbol and Name	Rorc, RAR-related orphan receptor gamma
Gene Synonym(s)
Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	EGFP expression is reported in the thymus (cortex) of adult mice. EGFP is expressed in double-positive thymocytes, with small amounts of EGFP in CD4⁺ and CD8⁺ single-positive thymocytes.
Strain of Origin	129P2/OlaHsd
Chromosome	3
Molecular Note	An isoform-specific disruption was generated by inserting a cassette containing eGFP downstream of the start codon of exon 1gammat. The targeted exon is the third exon of the gene, serves as an alternative first exon for the gammat transcript, and is not included in the gamma transcript. RT-PCR analysis of hepatic RNA obtained from homozygous mutant mice identified gamma transcript but not the targted gammat transcript. The eGFP sequence included a stop codon but no splice sites or polyadenylation signals. A floxed neo cassette included in the targeting vector was excised from the germline via cre-mediated recombination.
Mutations Made By	Dr. Dan Littman, New York University Medical Center

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - specific T cell deficiency
- Fluorescent Proteins
- Apoptosis Research
- Developmental Biology Research
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
- Growth Factors/Receptors/Cytokines
- Immunodeficiency
  - specific T cell deficiency
- Lymphoid Tissue Defects
  - hematopoietic development
  - selective lymph node development defects
Internal/Organ Research
- Gastrointestinal Defects
- Lymphoid Tissue Defects
  - T cell deficiency
- Thymus Defects
Developmental Biology Research
- Internal/Organ Defects
  - Lymphoid Tissue Defects
- Lymphoid Tissue Defects
  - hematopoietic defects
Apoptosis Research
- Endogenous Regulators
Cancer Research
- Growth Factors/Receptors/Cytokines

Mammalian Phenotype Terms by Genotype

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

Genotype: Rorc^tm2Litt/Rorc^tm2Litt
involves: 129P2/OlaHsd

cellular phenotype

increased thymocyte apoptosis
- isolated thymocytes undergo apoptosis in culture within 2-3 hours compared to controls that survive for more than 5 hours

immune system phenotype

abnormal lymph organ development
- absence of lymphoid tissue inducer (LTi) cells

absent Peyer's patches

decreased double-negative T cell number
- numbers of intestinal alpha beta T cells including CD4^-CD8^- cells are significantly reduced

abnormal CD4-positive, alpha-beta intraepithelial T cell morphology
- numbers of intestinal alpha beta T cells including CD4⁺ cells are significantly reduced

abnormal gut-associated lymphoid tissue morphology
- intestinal cryptopatches and isolated lymphoid follicles are absent
- absence of lymphoid tissue inducer (LTi) cells

decreased NK cell number
- the percentage and absolute numbers of the Ncr(NKp46)⁺CD127⁺NK1.1^- subset of intestinal natural killer cells is strongly decreased compared to controls
- Normal - however, the number of NK1.1⁺ subset of intestinal natural killer cells is normal

increased thymocyte apoptosis
- isolated thymocytes undergo apoptosis in culture within 2-3 hours compared to controls that survive for more than 5 hours

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology
- numbers of intestinal alpha beta T cells including CD8alpha-beta⁺ and CD8alpha-alpha⁺ cells are significantly reduced

decreased double-positive T cell number
- fewer double-positive T cells (30-50% that of wild-type)

absent lymph nodes
- mice lack all lymph nodes

endocrine/exocrine gland phenotype

increased thymocyte apoptosis
- isolated thymocytes undergo apoptosis in culture within 2-3 hours compared to controls that survive for more than 5 hours

hematopoietic system phenotype

increased thymocyte apoptosis
- isolated thymocytes undergo apoptosis in culture within 2-3 hours compared to controls that survive for more than 5 hours

decreased NK cell number
- the percentage and absolute numbers of the Ncr(NKp46)⁺CD127⁺NK1.1^- subset of intestinal natural killer cells is strongly decreased compared to controls
- Normal - however, the number of NK1.1⁺ subset of intestinal natural killer cells is normal

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology
- numbers of intestinal alpha beta T cells including CD8alpha-beta⁺ and CD8alpha-alpha⁺ cells are significantly reduced

decreased double-negative T cell number
- numbers of intestinal alpha beta T cells including CD4^-CD8^- cells are significantly reduced

decreased double-positive T cell number
- fewer double-positive T cells (30-50% that of wild-type)

abnormal CD4-positive, alpha-beta intraepithelial T cell morphology
- numbers of intestinal alpha beta T cells including CD4⁺ cells are significantly reduced

References

Eberl G; Marmon S; Sunshine MJ; Rennert PD; Choi Y; Littman DR. 2004. An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol 5(1):64-73PubMed: 14691482 MGI: J:87395
Ivanov II; McKenzie BS; Zhou L; Tadokoro CE; Lepelley A; Lafaille JJ; Cua DJ; Littman DR. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126(6):1121-33PubMed: 16990136 MGI: J:115922

Additional - Rorc^tm2Litt related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Rorc
- Standard PCR:Rorc
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

Although homozygous mice are fertile, they have increased thymoma incidence.

The donating investigator reports 80-90% of homozygotes succumb to thymomas by 12-14 weeks of age. It should be noted that the time to onset may vary due to vivarium-specific environmental factors. In the JAX Repository colony, we have observed that female homozygotes live to 9-11 weeks of age and most male homozygotes die before 8 months of age (October 2015). Some researchers observe a much earlier onset.

The Jackson Laboratory Repository maintains its live colony by breeding heterozygous mice with homozygous mice.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Homozygote
Citation
When using the Rorc(γt)-EGFP mouse strain in a publication, please cite the originating article(s) and include JAX stock #007572 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or Wild-Type for Rorc<tm2Litt>

Related Products and Services

Frozen Mouse Embryo	B6.129P2(Cg)-Rorc<tm2Litt>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2(Cg)-Rorc<tm2Litt>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2(Cg)-Rorc<tm2Litt>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129P2(Cg)-Rorc<tm2Litt>/J Frozen Embryo	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Rorc(γt)-EGFP

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Rorctm2Litt

Allele Symbol: Rorctm2Litt

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Rorctm2Litt/Rorctm2Littinvolves: 129P2/OlaHsd

cellular phenotype

immune system phenotype

endocrine/exocrine gland phenotype

hematopoietic system phenotype

References

Additional - Rorctm2Litt related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Rorc^tm2Litt

Allele Symbol: Rorc^tm2Litt

Genotype: Rorc^tm2Litt/Rorc^tm2Litt
involves: 129P2/OlaHsd

Additional - Rorc^tm2Litt related