These RORγ 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.
Dr. Dan R. Littman, New York University Medical Center
Mice homozygous for this retinoic acid-related orphan receptor gamma (RORgamma or RORγ) mutant allele are viable and fertile. The donating investigator reports that protein and mRNA from the targeted gene are undetectable in the thymus and other organs, and expression of both the RORγ and thymus-specific RORγ isoform (RORγt) are absent from homozygous tissue. Although homozygotes contain largely normal splenic architecture, they have a hypocellular thymus with abnormal development of lymph nodes and Peyer's patches, and lose thymic expression of the anti-apoptotic factor Bcl-xL. Mice with RORγt-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. These RORγ 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.
A targeting vector was designed to replace exon 4 (encoding the DNA-binding
domain) of the targeted gene with the neomycin resistance gene. The construct was electroporated into the 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric mice were bred to C57BL/6J. Heterozygotes were backcrossed to C57BL/6 mice for at least 10 generations prior to arrival at The Jackson Laboratory (see SNP note below). The Y chromosome may not have been fixed to the C57BL/6 genetic background.
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, all 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 C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Dan R Littman|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Dan R Littman; Rorctm1Litt|
|Gene Symbol and Name||Rorc, RAR-related orphan receptor gamma|
|Gene Synonym(s)||RORG; RORgamma; RZRG; NR1F3; thymus orphan receptor; thymus orphan receptor; Thor; TOR; Thor; RZR-GAMMA; IMD42|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A 200 bp fragment of the gene containing the exon encoding the DNA-binding domain was replaced with a neomycin resistance cassette via homologous recombination. Gene expression was undetectable in various tissues from homozygous mutant animals as determined by Northern blot analysis using a full-length cDNA probe. Western blot analysis did not detect protein expression in thymus of homozygous mutants.|
|Mutations Made By|| |
Dr. Dan Littman, New York University Medical Center
Although homozygous mice are fertile, they have increased thymoma incidence. The Jackson Laboratory Repository maintains its live colony by breeding heterozygous mice together, to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). We may also breed heterozygous mice with homozygous mice.
When using the RORγt-KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #007571 in your Materials and Methods section.
|Heterozygous or wildtype for Rorc<tm1Litt>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (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. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON 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, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES 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 JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or SERVICES by JACKSON.