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Strain Name: |
B6.129P2(Cg)-Rorctm2Litt/J |
Stock Number: |
007572 |
Availability:
| Under Development for Distribution Colony |
| To register your interest in this strain go to the Strain Interest Form. |
Product Information
Strain Details
| Type |
JAX® GEMM® Strain -
Congenic |
| Additional information on
JAX® GEMM® Strains. |
| Type |
JAX® GEMM® Strain -
Mutant Strain |
| Type |
JAX® GEMM® Strain -
Targeted Mutation |
| Mating System | +/+ sibling x Heterozygote
(Female x Male) |
|---|
| |
| Species | laboratory mouse |
| Donating Investigator | Dan Littman, New York University Medical Center |
| Generation | N6+
(16-APR-08)
|
|
|
Strain Description
Mice homozygous for this Rorc(gtGFP (or RORgt)GFP) mutant allele are viable and fertile. While Rorcg mRNA is detected in liver in Rorc(g)tGFP homozygotes, mRNA and protein for the thymus-specific isoform (Rorcgt) encoded by the targeted allele are not detected in the thymus. EGFP expression reports Rorc(gt) transcription in the thymi of adult Rorc(gt)GFP mice. Homozygous mice exhibit abnormal lymph node, Peyer's patch, and lymphoid tissue inducer (LTi) cell development. Mice with Rorcgt-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 RorcgtGFP 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.
Strain 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 1gt" 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(gt)GFPneo heterozygotes. These mice were then crossed with a Cre-deleter strain (unspecified genetic background) to excise the neo cassette. The resulting Rorc(gt)GFP pups were then backcrossed to C57BL/6 for at least 5 generations prior to arrival at The Jackson Laboratory. The Y chromosome may not have been fixed to the C57BL/6 genetic background.
Mammalian Phenotype Terms 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
(J:91566)
- numbers of intestinal alpha beta T cells including CD4+ cells are significantly reduced
- abnormal CD8 positive, alpha-beta intraepithelial T cell morphology
(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
(J:91566)
- numbers of intestinal alpha beta T cells including CD4-CD8- cells are significantly reduced
- immune system phenotype
- abnormal immune system morphology
(J:87395)
- absence of lymphoid inducer cells
- abnormal CD4-positive, alpha-beta intraepithelial T cell morphology
(J:91566)
- numbers of intestinal alpha beta T cells including CD4+ cells are significantly reduced
- abnormal CD8 positive, alpha-beta intraepithelial T cell morphology
(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
(J:91566)
- intestinal cryptopatches and isolated lymphoid follicles are absent
- absent lymph nodes
(J:87395)
- mice lacked all lymph nodes
- decreased double-negative T cell number
(J:91566)
- numbers of intestinal alpha beta T cells including CD4-CD8- cells are significantly reduced
|
Gene & Allele Details
| Allele Symbol |
Rorctm2Litt |
| Allele Name |
targeted mutation 2, Dan R Littman |
| Common Name(s) |
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 |
| Gene Symbol and Name |
Rorc, RAR-related orphan receptor gamma |
| Chromosome |
3 |
| Gene Common Name(s) |
MGC129539;
NR1F3;
RORG;
RORgamma;
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. [J:87395]
|
Control Information
Colony Maintenance
| Breeding & Husbandry | When maintaining a live colony, heterozygous or homozygous mice may be bred. |
| Diet Information |
LabDiet® 5K52/5K67
|
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View Fluorescent Protein Strains (135 strains)
Additional Web Information
Congenic Nomenclature
Fluorescent Proteins/lacZ Systems
Research Applications
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)
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]
[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]
[J:115922]
Additional References
Price and Supply Information
| Strain Name: |
B6.129P2(Cg)-Rorctm2Litt/J |
| Stock Number: |
007572 |
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:
02-JUN-08
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.
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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