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| These RorcγtGFP mutant mice may be useful in studying immune system homeostasis, T cell repertoire selection, CD4/CD8 double positive (CD4+/CD8+) thymocyte survival, lymphoid organogenesis, proinflammatory T-helper cell (Th17) development, mucosal immunology, and the role of inflammatory disease in autoimmunity and cancer progression. | |||||||||||
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Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System +/+ sibling x Heterozygote (Female x Male) 12-MAR-08 Species laboratory mouse Generation N6+N1F2 (30-DEC-08) Donating Investigator Dan Littman, New York University Medical Center Description
Mice homozygous for this Rorc(γtGFP (or RORγt)GFP) mutant allele are viable and fertile. While Rorcγ mRNA is detected in liver in Rorc(γ)tGFP 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 with age in homozygotes. These RorcγtGFP mutant mice may be useful in studying immune system homeostasis, T cell repertoire selection, CD4/CD8 double positive (CD4+/CD8+) thymocyte survival, lymphoid organogenesis, proinflammatory T-helper cell (Th17) development, mucosal immunology, 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 resulting Rorc(γt)GFP pups were then backcrossed to C57BL/6 for at least five generations prior to arrival at The Jackson Laboratory. The Y chromosome may not have been fixed to the C57BL/6 genetic background.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
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Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
- hematopoietic system phenotype
- abnormal CD4-positive, alpha-beta intraepithelial T cell morphology (MGI Ref ID J:91566)
- numbers of intestinal alpha beta T cells including CD4+ cells are significantly reduced
- abnormal CD8 positive, alpha-beta intraepithelial T cell morphology (MGI Ref ID J:91566)
- numbers of intestinal alpha beta T cells including CD8alpha-beta+ and CD8alpha-alpha+ cells are significantly reduced
- decreased NK cell number (MGI Ref ID J:142654)
- the percentage and absolute numbers of the Ncr(NKp46)+CD127+NK1.1- subset of intestinal natural killer cells is strongly decreased compared to controls
- however, the number of NK1.1+ subset of intestinal natural killer cells is normal
- decreased double-negative T cell number (MGI Ref ID J:91566)
- numbers of intestinal alpha beta T cells including CD4-CD8- cells are significantly reduced
- decreased double-positive T cell number (MGI Ref ID J:87395)
- fewer double-positive T cells (30-50% that of wild-type)
- immune system phenotype
- abnormal CD4-positive, alpha-beta intraepithelial T cell morphology (MGI Ref ID J:91566)
- numbers of intestinal alpha beta T cells including CD4+ cells are significantly reduced
- abnormal CD8 positive, alpha-beta intraepithelial T cell morphology (MGI Ref ID J:91566)
- numbers of intestinal alpha beta T cells including CD8alpha-beta+ and CD8alpha-alpha+ cells are significantly reduced
- abnormal gut-associated lymphoid tissue morphology (MGI Ref ID J:87395)
- absence of lymphoid tissue inducer (LTi) cells
- intestinal cryptopatches and isolated lymphoid follicles are absent
- absent Peyer's patches (MGI Ref ID J:87395)
- abnormal lymph organ development (MGI Ref ID J:87395)
- absence of lymphoid tissue inducer (LTi) cells
- absent lymph nodes (MGI Ref ID J:87395)
- mice lack all lymph nodes
- decreased NK cell number (MGI Ref ID J:142654)
- the percentage and absolute numbers of the Ncr(NKp46)+CD127+NK1.1- subset of intestinal natural killer cells is strongly decreased compared to controls
- however, the number of NK1.1+ subset of intestinal natural killer cells is normal
- decreased double-negative T cell number (MGI Ref ID J:91566)
- numbers of intestinal alpha beta T cells including CD4-CD8- cells are significantly reduced
- decreased double-positive T cell number (MGI Ref ID J:87395)
- fewer double-positive T cells (30-50% that of wild-type)
- increased thymocyte apoptosis (MGI Ref ID J:87395)
- isolated thymocytes undergo apoptosis in culture within 2-3 hours compared to controls that survive for more than 5 hours
This mouse can be used to support research in many areas including:
Apoptosis Research
Endogenous Regulators
Cancer Research
Growth Factors/Receptors/Cytokines
Developmental Biology Research
Internal/Organ Defects
Lymphoid Tissue Defects
Lymphoid Tissue Defects
hematopoietic defects
Immunology and Inflammation 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
Research Tools
Apoptosis Research
Developmental Biology Research
Fluorescent Proteins
Immunology and Inflammation Research
specific T cell deficiency
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Rorctm2Litt | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, Dan R Littman | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Roc(gt)gfp; Rorc(gammat)GFP; | ||
| Mutation Made By | Dan Littman, New York University Medical Center | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14 | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| 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. | ||
| Gene Symbol and Name | Rorc, RAR-related orphan receptor gamma | ||
| Chromosome | 3 | ||
| Gene Common Name(s) | MGC129539; MGC189525; NR1F3; RORG; RORgamma; RZR-GAMMA; RZRG; TOR; Thor; thymus orphan receptor; | ||
| 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 notincluded 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. [MGI Ref ID J:87395] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Fluorescent Proteins (Generic GFP), Melt Curve Analysis
Fluorescent Proteins (Generic GFP), Standard PCR
Rorctm2Litt, Melt Curve Analysis
Rorctm2Litt, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
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):64-73. [PubMed: 14691482] [MGI Ref ID 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):1121-33. [PubMed: 16990136] [MGI Ref ID J:115922]
Additional References
Rorctm2Litt relatedEberl G; Littman DR. 2004. Thymic origin of intestinal alphabeta T Cells Revealed by Fate Mapping of RORgammat+ Cells. Science 305(5681):248-51. [PubMed: 15247480] [MGI Ref ID J:91566]
Egawa T; Eberl G; Taniuchi I; Benlagha K; Geissmann F; Hennighausen L; Bendelac A; Littman DR. 2005. Genetic evidence supporting selection of the valpha14i NKT cell lineage from double-positive thymocyte precursors. Immunity 22(6):705-16. [PubMed: 15963785] [MGI Ref ID J:99111]
Luci C; Reynders A; Ivanov II; Cognet C; Chiche L; Chasson L; Hardwigsen J; Anguiano E; Banchereau J; Chaussabel D; Dalod M; Littman DR; Vivier E; Tomasello E. 2009. Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin. Nat Immunol 10(1):75-82. [PubMed: 19029904] [MGI Ref ID J:142347]
Nowak EC; Weaver CT; Turner H; Begum-Haque S; Becher B; Schreiner B; Coyle AJ; Kasper LH; Noelle RJ. 2009. IL-9 as a mediator of Th17-driven inflammatory disease. J Exp Med 206(8):1653-60. [PubMed: 19596803] [MGI Ref ID J:151590]
Ribot JC; deBarros A; Pang DJ; Neves JF; Peperzak V; Roberts SJ; Girardi M; Borst J; Hayday AC; Pennington DJ; Silva-Santos B. 2009. CD27 is a thymic determinant of the balance between interferon-gamma- and interleukin 17-producing gammadelta T cell subsets. Nat Immunol 10(4):427-36. [PubMed: 19270712] [MGI Ref ID J:148001]
Sanos SL; Bui VL; Mortha A; Oberle K; Heners C; Johner C; Diefenbach A. 2009. RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol 10(1):83-91. [PubMed: 19029903] [MGI Ref ID J:142348]
Satoh-Takayama N; Vosshenrich CA; Lesjean-Pottier S; Sawa S; Lochner M; Rattis F; Mention JJ; Thiam K; Cerf-Bensussan N; Mandelboim O; Eberl G; Di Santo JP. 2008. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29(6):958-70. [PubMed: 19084435] [MGI Ref ID J:142654]
Sharma MD; Hou DY; Liu Y; Koni PA; Metz R; Chandler P; Mellor AL; He Y; Munn DH. 2009. Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood 113(24):6102-11. [PubMed: 19366986] [MGI Ref ID J:149490]
Tsuji M; Komatsu N; Kawamoto S; Suzuki K; Kanagawa O; Honjo T; Hori S; Fagarasan S. 2009. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 323(5920):1488-92. [PubMed: 19286559] [MGI Ref ID J:145906]
Tsuji M; Suzuki K; Kitamura H; Maruya M; Kinoshita K; Ivanov II; Itoh K; Littman DR; Fagarasan S. 2008. Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin a generation in the gut. Immunity 29(2):261-71. [PubMed: 18656387] [MGI Ref ID J:139002]
Zhou L; Ivanov II; Spolski R; Min R; Shenderov K; Egawa T; Levy DE; Leonard WJ; Littman DR. 2007. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8(9):967-74. [PubMed: 17581537] [MGI Ref ID J:124293]
Zhou L; Lopes JE; Chong MM; Ivanov II; Min R; Victora GD; Shen Y; Du J; Rubtsov YP; Rudensky AY; Ziegler SF; Littman DR. 2008. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 453(7192):236-40. [PubMed: 18368049] [MGI Ref ID J:136164]
Zindl CL; Kim TH; Zeng M; Archambault AS; Grayson MH; Choi K; Schreiber RD; Chaplin DD. 2009. The lymphotoxin LTalpha(1)beta(2) controls postnatal and adult spleen marginal sinus vascular structure and function. Immunity 30(3):408-20. [PubMed: 19303389] [MGI Ref ID J:147033]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous or homozygous mice may be bred. Mating System +/+ sibling x Heterozygote (Female x Male) 12-MAR-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $243.50 Female or Male Heterozygous for Rorctm2Litt
Pairs /Price (US dollars $) Pair Genotype $297.85 Heterozygous for Rorctm2Litt x Wild-type for Rorctm2Litt $297.85 Wild-type for Rorctm2Litt x Heterozygous for Rorctm2Litt
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Heterozygous for Rorctm2Litt
Pairs /Price (US dollars $) Pair Genotype $387.30 Heterozygous for Rorctm2Litt x Wild-type for Rorctm2Litt $387.30 Wild-type for Rorctm2Litt x Heterozygous for Rorctm2Litt
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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