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)||Rorc-; Rorctm1Drl; RORgamma-|
|Gene Symbol and Name||Rorc, RAR-related orphan receptor gamma|
|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.
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