Strain Name:

B6.129P2-Rorctm1Litt/J

Stock Number:

007571

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
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.

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 SystemHeterozygote x Heterozygote         (Female x Male)   26-FEB-14
Specieslaboratory mouse
GenerationN20+pN1 (26-FEB-14)
Generation Definitions
 
Donating InvestigatorDr. Dan R. Littman,   New York University Medical Center

Description
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.

Development
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.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Rorc
008771   B6(Cg)-Rorctm3Litt/J
007572   B6.129P2(Cg)-Rorctm2Litt/J
022791   B6.FVB-Tg(Rorc-cre)1Litt/J
View Strains carrying other alleles of Rorc     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Rorctm1Litt/Rorctm1Litt

        involves: 129P2/OlaHsd
  • mortality/aging
  • increased susceptibility to bacterial infection induced morbidity/mortality
    • highly susceptible to C. rodentium and all die at day 10-12 post infection   (MGI Ref ID J:158663)
  • hematopoietic system phenotype
  • abnormal T cell differentiation
    • primary rearrangement of 5' Jalpha segments is reduced to 54% and central Jalpha segments is reduced 18.2%   (MGI Ref ID J:128344)
  • immune system phenotype
  • abnormal T cell differentiation
    • primary rearrangement of 5' Jalpha segments is reduced to 54% and central Jalpha segments is reduced 18.2%   (MGI Ref ID J:128344)
  • colitis
    • inflammation, and edema post infection with C. rodentium   (MGI Ref ID J:158663)
  • increased susceptibility to bacterial infection
    • display weight loss, colitis and severe disruption of the epithelial layer in the colon after infection with Citrobacter rodentium   (MGI Ref ID J:158663)
    • increased susceptibility to bacterial infection induced morbidity/mortality
      • highly susceptible to C. rodentium and all die at day 10-12 post infection   (MGI Ref ID J:158663)
  • growth/size/body phenotype
  • weight loss
    • exhibit weight loss post infection with C. rodentium   (MGI Ref ID J:158663)
  • digestive/alimentary phenotype
  • abnormal colon morphology
    • severe disruption of the epithelial layer post infection with C. rodentium   (MGI Ref ID J:158663)
    • colonic necrosis
      • multifocal necrosis in colon post infection with C. rodentium   (MGI Ref ID J:158663)
  • colitis
    • inflammation, and edema post infection with C. rodentium   (MGI Ref ID J:158663)
View Research Applications

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, Inflammation and Autoimmunity 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
Cancer Research
      specific T cell deficiency
Developmental Biology Research
Immunology, Inflammation and Autoimmunity Research
      specific T cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Rorctm1Litt
Allele Name targeted mutation 1, Dan R Littman
Allele Type Targeted (Null/Knockout)
Common Name(s) RORgamma-; Rorc-; Rorctm1Drl;
Mutation Made ByDr. Dan Littman,   New York University Medical Center
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Rorc, RAR-related orphan receptor gamma
Chromosome 3
Gene Common Name(s) NR1F3; RORG; RORgamma; RZR-GAMMA; RZRG; TOR; Thor; thymus orphan receptor;
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. [MGI Ref ID J:63146]

Genotyping

Genotyping Information

Genotyping Protocols

Rorctm1Litt, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Sun Z; Unutmaz D; Zou YR; Sunshine MJ; Pierani A; Brenner-Morton S; Mebius RE; Littman DR. 2000. Requirement for RORgamma in thymocyte survival and lymphoid organ development. Science 288(5475):2369-73. [PubMed: 10875923]  [MGI Ref ID J:63146]

Additional References

Rorctm1Litt related

Abarrategui I; Krangel MS. 2007. Noncoding transcription controls downstream promoters to regulate T-cell receptor alpha recombination. EMBO J 26(20):4380-90. [PubMed: 17882258]  [MGI Ref ID J:128344]

Benezech C; White A; Mader E; Serre K; Parnell S; Pfeffer K; Ware CF; Anderson G; Caamano JH. 2010. Ontogeny of stromal organizer cells during lymph node development. J Immunol 184(8):4521-30. [PubMed: 20237296]  [MGI Ref ID J:159868]

Bezbradica JS; Hill T; Stanic AK; Van Kaer L; Joyce S. 2005. Commitment toward the natural T (iNKT) cell lineage occurs at the CD4+8+ stage of thymic ontogeny. Proc Natl Acad Sci U S A 102(14):5114-9. [PubMed: 15792999]  [MGI Ref ID J:97416]

Buonocore S; Ahern PP; Uhlig HH; Ivanov II; Littman DR; Maloy KJ; Powrie F. 2010. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464(7293):1371-5. [PubMed: 20393462]  [MGI Ref ID J:159460]

Chappaz S; Finke D. 2010. The IL-7 signaling pathway regulates lymph node development independent of peripheral lymphocytes. J Immunol 184(7):3562-9. [PubMed: 20207995]  [MGI Ref ID J:160069]

Dudakov JA; Hanash AM; Jenq RR; Young LF; Ghosh A; Singer NV; West ML; Smith OM; Holland AM; Tsai JJ; Boyd RL; van den Brink MR. 2012. Interleukin-22 drives endogenous thymic regeneration in mice. Science 336(6077):91-5. [PubMed: 22383805]  [MGI Ref ID J:182233]

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]

Fulton LM; Carlson MJ; Coghill JM; Ott LE; West ML; Panoskaltsis-Mortari A; Littman DR; Blazar BR; Serody JS. 2012. Attenuation of acute graft-versus-host disease in the absence of the transcription factor RORgammat. J Immunol 189(4):1765-72. [PubMed: 22778391]  [MGI Ref ID J:189760]

Hager E; Hawwari A; Matsuda JL; Krangel MS; Gapin L. 2007. Multiple constraints at the level of TCRalpha rearrangement impact Valpha14i NKT cell development. J Immunol 179(4):2228-34. [PubMed: 17675483]  [MGI Ref ID J:151224]

Hawwari A; Bock C; Krangel MS. 2005. Regulation of T cell receptor alpha gene assembly by a complex hierarchy of germline Jalpha promoters. Nat Immunol 6(5):481-9. [PubMed: 15806105]  [MGI Ref ID J:97736]

Hawwari A; Krangel MS. 2007. Role for rearranged variable gene segments in directing secondary T cell receptor alpha recombination. Proc Natl Acad Sci U S A 104(3):903-7. [PubMed: 17210914]  [MGI Ref ID J:119067]

Hess PR; Rawnsley DR; Jakus Z; Yang Y; Sweet DT; Fu J; Herzog B; Lu M; Nieswandt B; Oliver G; Makinen T; Xia L; Kahn ML. 2014. Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life. J Clin Invest 124(1):273-84. [PubMed: 24292710]  [MGI Ref ID J:207924]

Hikosaka Y; Nitta T; Ohigashi I; Yano K; Ishimaru N; Hayashi Y; Matsumoto M; Matsuo K; Penninger JM; Takayanagi H; Yokota Y; Yamada H; Yoshikai Y; Inoue J; Akiyama T; Takahama Y. 2008. The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity 29(3):438-50. [PubMed: 18799150]  [MGI Ref ID J:139648]

Leppkes M; Becker C; Ivanov II; Hirth S; Wirtz S; Neufert C; Pouly S; Murphy AJ; Valenzuela DM; Yancopoulos GD; Becher B; Littman DR; Neurath MF. 2009. RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F. Gastroenterology 136(1):257-67. [PubMed: 18992745]  [MGI Ref ID J:159748]

Meier D; Bornmann C; Chappaz S; Schmutz S; Otten LA; Ceredig R; Acha-Orbea H; Finke D. 2007. Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity 26(5):643-54. [PubMed: 17521585]  [MGI Ref ID J:123554]

Powolny-Budnicka I; Riemann M; Tanzer S; Schmid RM; Hehlgans T; Weih F. 2011. RelA and RelB Transcription Factors in Distinct Thymocyte Populations Control Lymphotoxin-Dependent Interleukin-17 Production in gammadelta T Cells. Immunity 34(3):364-74. [PubMed: 21419662]  [MGI Ref ID J:169863]

Rangel-Moreno J; Moyron-Quiroz JE; Carragher DM; Kusser K; Hartson L; Moquin A; Randall TD. 2009. Omental milky spots develop in the absence of lymphoid tissue-inducer cells and support B and T cell responses to peritoneal antigens. Immunity 30(5):731-43. [PubMed: 19427241]  [MGI Ref ID J:149548]

Roberts NA; White AJ; Jenkinson WE; Turchinovich G; Nakamura K; Withers DR; McConnell FM; Desanti GE; Benezech C; Parnell SM; Cunningham AF; Paolino M; Penninger JM; Simon AK; Nitta T; Ohigashi I; Takahama Y; Caamano JH; Hayday AC; Lane PJ; Jenkinson EJ;Anderson G. 2012. Rank signaling links the development of invariant gammadelta T cell progenitors and Aire(+) medullary epithelium. Immunity 36(3):427-37. [PubMed: 22425250]  [MGI Ref ID J:187054]

Schmolka N; Serre K; Grosso AR; Rei M; Pennington DJ; Gomes AQ; Silva-Santos B. 2013. Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory gammadelta T cell subsets. Nat Immunol 14(10):1093-100. [PubMed: 23995235]  [MGI Ref ID J:208217]

Schmutz S; Bosco N; Chappaz S; Boyman O; Acha-Orbea H; Ceredig R; Rolink AG; Finke D. 2009. Cutting edge: IL-7 regulates the peripheral pool of adult RORgamma+ lymphoid tissue inducer cells. J Immunol 183(4):2217-21. [PubMed: 19635901]  [MGI Ref ID J:151481]

Shibata K; Yamada H; Sato T; Dejima T; Nakamura M; Ikawa T; Hara H; Yamasaki S; Kageyama R; Iwakura Y; Kawamoto H; Toh H; Yoshikai Y. 2011. Notch-Hes1 pathway is required for the development of IL-17-producing {gamma}{delta} T cells. Blood 118(3):586-93. [PubMed: 21606479]  [MGI Ref ID J:174874]

Suzukawa M; Morita H; Nambu A; Arae K; Shimura E; Shibui A; Yamaguchi S; Suzukawa K; Nakanishi W; Oboki K; Kajiwara N; Ohno T; Ishii A; Korner H; Cua DJ; Suto H; Yoshimoto T; Iwakura Y; Yamasoba T; Ohta K; Sudo K; Saito H; Okumura K; Broide DH; MatsumotoK; Nakae S. 2012. Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma. J Immunol 189(7):3641-52. [PubMed: 22942422]  [MGI Ref ID J:190342]

Wang R; Xie H; Huang Z; Ma J; Fang X; Ding Y; Sun Z. 2011. T cell factor 1 regulates thymocyte survival via a RORgammat-dependent pathway. J Immunol 187(11):5964-73. [PubMed: 22039299]  [MGI Ref ID J:179753]

Wang Y; Koroleva EP; Kruglov AA; Kuprash DV; Nedospasov SA; Fu YX; Tumanov AV. 2010. Lymphotoxin beta receptor signaling in intestinal epithelial cells orchestrates innate immune responses against mucosal bacterial infection. Immunity 32(3):403-13. [PubMed: 20226692]  [MGI Ref ID J:158663]

White AJ; Withers DR; Parnell SM; Scott HS; Finke D; Lane PJ; Jenkinson EJ; Anderson G. 2008. Sequential phases in the development of Aire-expressing medullary thymic epithelial cells involve distinct cellular input. Eur J Immunol 38(4):942-7. [PubMed: 18350550]  [MGI Ref ID J:133775]

Yang CY; Vogt TK; Favre S; Scarpellino L; Huang HY; Tacchini-Cottier F; Luther SA. 2014. Trapping of naive lymphocytes triggers rapid growth and remodeling of the fibroblast network in reactive murine lymph nodes. Proc Natl Acad Sci U S A 111(1):E109-18. [PubMed: 24367096]  [MGI Ref ID J:206381]

Yuan J; Crittenden RB; Bender TP. 2010. c-Myb promotes the survival of CD4+CD8+ double-positive thymocytes through upregulation of Bcl-xL. J Immunol 184(6):2793-804. [PubMed: 20142358]  [MGI Ref ID J:160124]

Zhang N; Guo J; He YW. 2003. Lymphocyte accumulation in the spleen of retinoic acid receptor-related orphan receptor gamma-deficient mice. J Immunol 171(4):1667-75. [PubMed: 12902464]  [MGI Ref ID J:84805]

van de Pavert SA; Ferreira M; Domingues RG; Ribeiro H; Molenaar R; Moreira-Santos L; Almeida FF; Ibiza S; Barbosa I; Goverse G; Labao-Almeida C; Godinho-Silva C; Konijn T; Schooneman D; O'Toole T; Mizee MR; Habani Y; Haak E; Santori FR; Littman DR; Schulte-Merker S; Dzierzak E; Simas JP; Mebius RE; Veiga-Fernandes H. 2014. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity. Nature 508(7494):123-7. [PubMed: 24670648]  [MGI Ref ID J:208884]

von Burg N; Chappaz S; Baerenwaldt A; Horvath E; Bose Dasgupta S; Ashok D; Pieters J; Tacchini-Cottier F; Rolink A; Acha-Orbea H; Finke D. 2014. Activated group 3 innate lymphoid cells promote T-cell-mediated immune responses. Proc Natl Acad Sci U S A 111(35):12835-40. [PubMed: 25136120]  [MGI Ref ID J:214818]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryAlthough 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.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   26-FEB-14

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHeterozygous for Rorctm1Litt  
$232.00Female or MaleHomozygous for Rorctm1Litt  
Price per Pair (US dollars $)Pair Genotype
$464.00Heterozygous for Rorctm1Litt x Heterozygous for Rorctm1Litt  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Rorctm1Litt  
$301.60Female or MaleHomozygous for Rorctm1Litt  
Price per Pair (US dollars $)Pair Genotype
$603.20Heterozygous for Rorctm1Litt x Heterozygous for Rorctm1Litt  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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"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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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