| |||||||||
| 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. | |||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Heterozygote (Female x Male) Species laboratory mouse Generation N6+N1F1 (16-MAY-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 | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (170 strains)
Additional Web Information
Congenic Nomenclature
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 double-negative T cell number (MGI Ref ID J:91566)
- numbers of intestinal alpha beta T cells including CD4-CD8- cells are significantly reduced
- immune system phenotype
- abnormal immune system morphology (MGI Ref ID J:87395)
- absence of lymphoid inducer cells
- 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:91566)
- intestinal cryptopatches and isolated lymphoid follicles are absent
- absent Peyer's patches (MGI Ref ID J:87395)
- absent lymph nodes (MGI Ref ID J:87395)
- mice lacked all lymph nodes
- 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
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)
Lymphoid Tissue Defects (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), MCA, vers. 2
Fluorescent Proteins (Generic GFP), STD PCR, vers. 1
Rorctm2Litt, MCA, vers. 2
Rorctm2Litt, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
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]
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]
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) 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* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Heterozygous for Rorctm2Litt *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Heterozygous for Rorctm2Litt x Wild-type for Rorctm2Litt $288.65 Wild-type for Rorctm2Litt x Heterozygous for Rorctm2Litt
Additional Supply Details
| Supply Notes |
|
|---|
| Pricing for International shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Heterozygous for Rorctm2Litt *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Heterozygous for Rorctm2Litt x Wild-type for Rorctm2Litt $375.30 Wild-type for Rorctm2Litt x Heterozygous for Rorctm2Litt
Additional Supply Details
| Supply Notes |
|
|---|
|
|
|
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 ~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 48 hours of order placement. |
|---|---|
| Supply Notes |
|
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. | ||
General Terms and Conditions
See Terms of Use
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.Ordering and Purchasing Information
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form
Terms of Use
Terms of Use
General Terms and Conditions
Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
Contact information
General inquiries
Contracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice & Services Conditions of Use
“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”No Warranty
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. THE LABORATORY EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.
No Liability
In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.
MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.
Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.