Strain Name:

B6.Cg-Tg(Cd4-TGFBR2)16Flv/J

Stock Number:

005551

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Availability:

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Use Restrictions Apply, see Terms of Use
The expression of a dominant-negative form of the human transforming growth factor (TGF), beta receptor II under the direction of the mouse CD4 antigen promoter in these transgenic mice blocks TGF-beta signaling specifically in CD4+ and CD8+ T cells. This mutant mouse strain may be useful in studies of autoimmune disease, anti-tumor immune response, and inflammatory bowel disease.

Description

Strain Information

Type Congenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemInbred x Hemizygote         (Female x Male)   27-JUN-06
Specieslaboratory mouse
GenerationN15+N17 (30-JUN-11)
Generation Definitions
 
Donating InvestigatorDr. Richard A. Flavell,   Yale University School of Medicine

Description
These transgenic mice express a dominant-negative form of the human transforming growth factor, beta receptor II (dnTGFBRII) under the direction of the mouse CD4 antigen promoter. Transgene expression is detected by RT-PCR analysis of thymus tissue, and is at a level sufficient to block TGF-beta signaling specifically in CD4+ and CD8+ T cells. At 3 to 4 months of age transgenic mice begin to display wasting and diarrhea. Histological examination reveals inflammatory bowel disease (IBD) and inflammatory infiltration of the large intestine, lungs, and liver. Less severe infiltration is observed in the stomach, duodenum, pancreas and kidney. The Donating Investigator indicates that the severity of and organs affected by the IBD is influenced by strain background. Western blot analysis detects circulating autoreactive antibodies. IgG immune deposits form in kidney glomeruli. There is a 3-fold increase in total cell numbers in peripheral lymphoid organs. T cells spontaneously differentiate into Th1 or Th2 cytokine secreting cells. Transgenic mice do not develop tumors when challenged with some TGF-beta producing tumor cells. Mice hemizygous for the transgenic insert are viable and fertile. Hemizygous female mice do not support pregnancies well. This mutant mouse strain may be useful in studies of autoimmune disease, anti-tumor immune response, and inflammatory bowel disease.

Development
A transgenic construct containing sequence between nucleotides -7 and +573 of the human transforming growth factor, beta receptor II (70/80kDa) gene under the direction of the mouse CD4 antigen promoter was microinjected into B6C3HF1 fertilized oocytes. The donating investigator reported that the resulting founder animals were backcrossed to B10.BR mice for 3 generations, then backcrossed to C57BL/6 mice for 15 generations (see SNP note below).

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, 1 of 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 mixed C57BL/6J ; C57BL/6N genetic background.

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Cd4
008126   B6.NOD-Tg(Cd4-EGFP)1Lt/J
004687   C.Cg-Tg(SKP2)4Paga/J
005334   NOD/ShiLt-Tg(Cd4-EGFP)1Lt/J
View Strains carrying other alleles of Cd4     (3 strains)

Strains carrying other alleles of TGFBR2
008378   B6.Cg-Tg(Itgax-TGFBR2)1Flv/J
View Strains carrying other alleles of TGFBR2     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Colorectal Cancer, Hereditary Nonpolyposis, Type 6; HNPCC6   (TGFBR2)
Esophageal Cancer   (TGFBR2)
Loeys-Dietz Syndrome 2; LDS2   (TGFBR2)
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.

Tg(Cd4-TGFBR2)16Flv/?

        involves: C3H * C57BL/6 * C57BL/10 * C57BR/cd
  • growth/size/body phenotype
  • cachexia
    • starting about 3 to 4 months of age, mice begin wasting due to an autoimmune disease   (MGI Ref ID J:97554)
  • immune system phenotype
  • abnormal T cell activation
    • all CD8 T cells and most CD4 T cells are in an activated, effector state with CD8 T cells producing IFN-gamma and CD4 T cells producing Th1 and/or Th2 cytokines   (MGI Ref ID J:97554)
    • abnormal T cell proliferation
      • in vitro stimulated CD4- and CD8- T cells are refractory to the inhibitory effects of TGF-beta1 and TGF-beta3 on T cell proliferation   (MGI Ref ID J:97554)
      • there is only a slight inhibition of proliferation on activated T cells by TGF-beta2   (MGI Ref ID J:97554)
  • abnormal thymus involution
    • thymuses of 5 month old mice are completely involuted with only thymic lymph nodes detectable in the area where the thymus in normally present   (MGI Ref ID J:97554)
  • decreased B cell number
    • there is a decrease in the percentage of B cells found in the spleen though due to the increase in spleen cellularity the total number of B cells is normal   (MGI Ref ID J:97554)
  • increased anti-nuclear antigen antibody level
    • auto-antibodies to nuclear proteins are detected in the sera of mice with specificity of these antibodies differing between individual mice   (MGI Ref ID J:97554)
  • increased immunoglobulin level   (MGI Ref ID J:97554)
    • increased IgA level
      • sera levels of IgA are 16 fold higher in 5-6 month old mice than in age matched wild-type mice   (MGI Ref ID J:97554)
    • increased IgG1 level
      • sera levels of IgG1 are 8 fold higher in 5-6 month old mice than in age matched wild-type mice   (MGI Ref ID J:97554)
    • increased IgG2a level
      • sera levels of IgG2a are 4 fold higher in 5-6 month old mice than in age matched wild-type mice   (MGI Ref ID J:97554)
  • increased inflammatory response   (MGI Ref ID J:97554)
    • colitis
      • pronounced inflammation in the gut is evident in 5 month old mice with dense infiltrates of lymphocytes, macrophages and plasma cells occurring in the lamina propia and mucosal epithelia   (MGI Ref ID J:97554)
      • the inflammation also causes distortion of the crypt architecture, crypt abscesses and compensatory epithelial hyperplasia   (MGI Ref ID J:97554)
      • mild inflammation is also evident in the stomach and duodenum   (MGI Ref ID J:97554)
    • glomerulonephritis
      • IgG deposits are found in the kidney glomeruli of 5 month old mice   (MGI Ref ID J:97554)
      • mild infiltration of inflammatory cells is also observed   (MGI Ref ID J:97554)
    • liver inflammation
      • there are clusters of macrophages and lymphocytes located in the parenchyma and adjacent to blood vessels in the liver of 5 month old mice   (MGI Ref ID J:97554)
    • lung inflammation
      • lungs of 5 month old mice have focal perivascular and intraalveolar infiltration of lymphocytes and macrophages   (MGI Ref ID J:97554)
    • pancreas inflammation
      • mild inflammation is evident in the pancreas of 5 month old mice   (MGI Ref ID J:97554)
  • increased memory T cell number
    • 90% of the T cells found in the spleen of 5 month old mice are CD62Llow CD44high indicating an activated/memory phenotype   (MGI Ref ID J:97554)
    • increases in memory T cell numbers are found as early as 4 weeks of age   (MGI Ref ID J:97554)
  • lymph node hyperplasia
    • there is a 3-fold increase in the number of cells found in the lymph nodes   (MGI Ref ID J:97554)
  • spleen hyperplasia
    • total cell number in the spleen is increased by about 60%   (MGI Ref ID J:97554)
  • digestive/alimentary phenotype
  • colitis
    • pronounced inflammation in the gut is evident in 5 month old mice with dense infiltrates of lymphocytes, macrophages and plasma cells occurring in the lamina propia and mucosal epithelia   (MGI Ref ID J:97554)
    • the inflammation also causes distortion of the crypt architecture, crypt abscesses and compensatory epithelial hyperplasia   (MGI Ref ID J:97554)
    • mild inflammation is also evident in the stomach and duodenum   (MGI Ref ID J:97554)
  • diarrhea
    • mice start developing diarrhea at about 3 to 4 months of age   (MGI Ref ID J:97554)
  • endocrine/exocrine gland phenotype
  • abnormal thymus involution
    • thymuses of 5 month old mice are completely involuted with only thymic lymph nodes detectable in the area where the thymus in normally present   (MGI Ref ID J:97554)
  • pancreas inflammation
    • mild inflammation is evident in the pancreas of 5 month old mice   (MGI Ref ID J:97554)
  • hematopoietic system phenotype
  • abnormal T cell activation
    • all CD8 T cells and most CD4 T cells are in an activated, effector state with CD8 T cells producing IFN-gamma and CD4 T cells producing Th1 and/or Th2 cytokines   (MGI Ref ID J:97554)
    • abnormal T cell proliferation
      • in vitro stimulated CD4- and CD8- T cells are refractory to the inhibitory effects of TGF-beta1 and TGF-beta3 on T cell proliferation   (MGI Ref ID J:97554)
      • there is only a slight inhibition of proliferation on activated T cells by TGF-beta2   (MGI Ref ID J:97554)
  • abnormal thymus involution
    • thymuses of 5 month old mice are completely involuted with only thymic lymph nodes detectable in the area where the thymus in normally present   (MGI Ref ID J:97554)
  • decreased B cell number
    • there is a decrease in the percentage of B cells found in the spleen though due to the increase in spleen cellularity the total number of B cells is normal   (MGI Ref ID J:97554)
  • increased immunoglobulin level   (MGI Ref ID J:97554)
    • increased IgA level
      • sera levels of IgA are 16 fold higher in 5-6 month old mice than in age matched wild-type mice   (MGI Ref ID J:97554)
    • increased IgG1 level
      • sera levels of IgG1 are 8 fold higher in 5-6 month old mice than in age matched wild-type mice   (MGI Ref ID J:97554)
    • increased IgG2a level
      • sera levels of IgG2a are 4 fold higher in 5-6 month old mice than in age matched wild-type mice   (MGI Ref ID J:97554)
  • increased memory T cell number
    • 90% of the T cells found in the spleen of 5 month old mice are CD62Llow CD44high indicating an activated/memory phenotype   (MGI Ref ID J:97554)
    • increases in memory T cell numbers are found as early as 4 weeks of age   (MGI Ref ID J:97554)
  • spleen hyperplasia
    • total cell number in the spleen is increased by about 60%   (MGI Ref ID J:97554)
  • liver/biliary system phenotype
  • liver inflammation
    • there are clusters of macrophages and lymphocytes located in the parenchyma and adjacent to blood vessels in the liver of 5 month old mice   (MGI Ref ID J:97554)
  • renal/urinary system phenotype
  • glomerulonephritis
    • IgG deposits are found in the kidney glomeruli of 5 month old mice   (MGI Ref ID J:97554)
    • mild infiltration of inflammatory cells is also observed   (MGI Ref ID J:97554)
  • respiratory system phenotype
  • lung inflammation
    • lungs of 5 month old mice have focal perivascular and intraalveolar infiltration of lymphocytes and macrophages   (MGI Ref ID J:97554)

Tg(Cd4-TGFBR2)16Flv/?

        involves: C3H * C57BL/6
  • digestive/alimentary phenotype
  • colitis
    • colitis is observed in mice 3-4 months of age with ulcerations found near the iliel-cecal junction, the ascending-to-descending colon transition and the anal-rectal junction   (MGI Ref ID J:134156)
  • immune system phenotype
  • abnormal CD8-positive, alpha-beta regulatory T cell morphology
    • CD8 T cells fail to express FoxP3 when cultured under conditions that normally generate regulatory CD8 T cells (high costimulation and TGF-beta signaling)   (MGI Ref ID J:134473)
  • abnormal T cell proliferation
    • TGF-beta is unable to increase proliferation of in vitro activated CD8 T cells   (MGI Ref ID J:134473)
  • colitis
    • colitis is observed in mice 3-4 months of age with ulcerations found near the iliel-cecal junction, the ascending-to-descending colon transition and the anal-rectal junction   (MGI Ref ID J:134156)
  • increased interferon-gamma secretion
    • there is an increase in the percentage of CD8 T cells producing IFN-gamma compared to wild-type mice there is an increase in the percentage of CD8 T cells producing IFN-gamma compared to wild-type mice   (MGI Ref ID J:134156)
  • increased tumor necrosis factor secretion
    • 32.6% of T cells produce TNF compared to 23.8% of wild-type mice   (MGI Ref ID J:134156)
  • hematopoietic system phenotype
  • abnormal CD8-positive, alpha-beta regulatory T cell morphology
    • CD8 T cells fail to express FoxP3 when cultured under conditions that normally generate regulatory CD8 T cells (high costimulation and TGF-beta signaling)   (MGI Ref ID J:134473)
  • abnormal T cell proliferation
    • TGF-beta is unable to increase proliferation of in vitro activated CD8 T cells   (MGI Ref ID J:134473)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Cancer Research
Tumor Resistance

Immunology, Inflammation and Autoimmunity Research
Inflammation
      Inflammatory bowel disease

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Cd4-TGFBR2)16Flv
Allele Name transgene insertion 16, Richard A Flavell
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) CD4-dnTGFBRII; CD4dn-TGF-RII; CD4dnTGFbetaRII; CD4dnTgfbr2; dnTGF-betaRII; dnTGFbetaRII; dnTbetaRII; dnTgfbr2+;
Mutation Made By Elizabeth Eynon,   Yale University School of Medicine, HHMI
Strain of OriginC57BL/6 x C3H
Expressed Gene TGFBR2, transforming growth factor, beta receptor II (70/80kDa), human
Promoter Cd4, Cd4 molecule, rat
General Note Phenotypic Similarity to Human Syndrome: Inflammatory Bowel Disease (J:134156) when this allele is on a Il10rbtm1Agt homozygote background.
Molecular Note This transgene contains the mouse CD4 antigen promoter, sequence encoding the extracellular and transmembrane regions, nucleotides -7 and +573, of the human transforming growth factor, beta receptor II (70/80kDa) and a polyadenylation signal. Transgene expression is detected by RT-PCR analysis of thymus tissue, and is at a level sufficient to block TGF-beta signaling specifically in T cells. [MGI Ref ID J:97554]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Cd4-TGFBR2)16Flv -Melt Curve Analysis, Melt Curve Analysis
Tg(Cd4-TGFBR2)16Flv, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Gorelik L; Flavell RA. 2000. Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 12(2):171-81. [PubMed: 10714683]  [MGI Ref ID J:97554]

Additional References

Tg(Cd4-TGFBR2)16Flv related

Allen SJ; Mott KR; Wechsler SL; Flavell RA; Town T; Ghiasi H. 2011. Adaptive and Innate Transforming Growth Factor {beta} Signaling Impact Herpes Simplex Virus 1 Latency and Reactivation. J Virol 85(21):11448-56. [PubMed: 21880769]  [MGI Ref ID J:177047]

Collison LW; Chaturvedi V; Henderson AL; Giacomin PR; Guy C; Bankoti J; Finkelstein D; Forbes K; Workman CJ; Brown SA; Rehg JE; Jones ML; Ni HT; Artis D; Turk MJ; Vignali DA. 2010. IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol 11(12):1093-101. [PubMed: 20953201]  [MGI Ref ID J:167328]

Coomes SM; Farmen S; Wilke CA; Laouar Y; Moore BB. 2011. Severe gammaherpesvirus-induced pneumonitis and fibrosis in syngeneic bone marrow transplant mice is related to effects of transforming growth factor-beta. Am J Pathol 179(5):2382-96. [PubMed: 21924228]  [MGI Ref ID J:180020]

Daley SR; Ma J; Adams E; Cobbold SP; Waldmann H. 2007. A key role for TGF-beta signaling to T cells in the long-term acceptance of allografts. J Immunol 179(6):3648-54. [PubMed: 17785800]  [MGI Ref ID J:152050]

De Paiva CS; Volpe EA; Gandhi NB; Zhang X; Zheng X; Pitcher JD 3rd; Farley WJ; Stern ME; Niederkorn JY; Li DQ; Flavell RA; Pflugfelder SC. 2011. Disruption of TGF-beta signaling improves ocular surface epithelial disease in experimental autoimmune keratoconjunctivitis sicca. PLoS One 6(12):e29017. [PubMed: 22194977]  [MGI Ref ID J:182352]

Diener KR; Woods AE; Manavis J; Brown MP; Hayball JD. 2009. Transforming growth factor-beta-mediated signaling in T lymphocytes impacts on prostate-specific immunity and early prostate tumor progression. Lab Invest 89(2):142-51. [PubMed: 19079323]  [MGI Ref ID J:144222]

Donkor MK; Sarkar A; Savage PA; Franklin RA; Johnson LK; Jungbluth AA; Allison JP; Li MO. 2011. T Cell Surveillance of Oncogene-Induced Prostate Cancer Is Impeded by T Cell-Derived TGF-beta1 Cytokine. Immunity 35(1):123-34. [PubMed: 21757379]  [MGI Ref ID J:174515]

Fan TM; Kranz DM; Flavell RA; Roy EJ. 2008. Costimulatory strength influences the differential effects of transforming growth factor beta1 for the generation of CD8(+) regulatory T cells. Mol Immunol 45(10):2937-50. [PubMed: 18321576]  [MGI Ref ID J:134473]

Filippi CM; Juedes AE; Oldham JE; Ling E; Togher L; Peng Y; Flavell RA; von Herrath MG. 2008. Transforming growth factor-beta suppresses the activation of CD8+ T-cells when naive but promotes their survival and function once antigen experienced: a two-faced impact on autoimmunity. Diabetes 57(10):2684-92. [PubMed: 18689691]  [MGI Ref ID J:142144]

Gao Y; Grassi F; Ryan MR; Terauchi M; Page K; Yang X; Weitzmann MN; Pacifici R. 2007. IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. J Clin Invest 117(1):122-32. [PubMed: 17173138]  [MGI Ref ID J:117462]

Garidou L; Heydari S; Gossa S; McGavern DB. 2012. Therapeutic blockade of transforming growth factor beta fails to promote clearance of a persistent viral infection. J Virol 86(13):7060-71. [PubMed: 22553324]  [MGI Ref ID J:186188]

Ghoreschi K; Laurence A; Yang XP; Tato CM; McGeachy MJ; Konkel JE; Ramos HL; Wei L; Davidson TS; Bouladoux N; Grainger JR; Chen Q; Kanno Y; Watford WT; Sun HW; Eberl G; Shevach EM; Belkaid Y; Cua DJ; Chen W; O'Shea JJ. 2010. Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 467(7318):967-71. [PubMed: 20962846]  [MGI Ref ID J:165551]

Gorelik L; Constant S; Flavell RA. 2002. Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation. J Exp Med 195(11):1499-505. [PubMed: 12045248]  [MGI Ref ID J:97553]

Gorelik L; Flavell RA. 2001. Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med 7(10):1118-22. [PubMed: 11590434]  [MGI Ref ID J:72218]

Guo Z; Khattar M; Schroder PM; Miyahara Y; Wang G; He X; Chen W; Stepkowski SM. 2013. A Dynamic Dual Role of IL-2 Signaling in the Two-Step Differentiation Process of Adaptive Regulatory T Cells. J Immunol 190(7):3153-62. [PubMed: 23427250]  [MGI Ref ID J:194525]

Huang G; Wang Y; Chi H. 2013. Control of T cell fates and immune tolerance by p38alpha signaling in mucosal CD103+ dendritic cells. J Immunol 191(2):650-9. [PubMed: 23752611]  [MGI Ref ID J:204825]

Izcue A; Hue S; Buonocore S; Arancibia-Carcamo CV; Ahern PP; Iwakura Y; Maloy KJ; Powrie F. 2008. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity 28(4):559-70. [PubMed: 18400195]  [MGI Ref ID J:134507]

Joffre O; Santolaria T; Calise D; Al Saati T; Hudrisier D; Romagnoli P; van Meerwijk JP. 2008. Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes. Nat Med 14(1):88-92. [PubMed: 18066074]  [MGI Ref ID J:130486]

Jones TG; Finkelman FD; Austen KF; Gurish MF. 2010. T regulatory cells control antigen-induced recruitment of mast cell progenitors to the lungs of C57BL/6 mice. J Immunol 185(3):1804-11. [PubMed: 20601599]  [MGI Ref ID J:162451]

Kang SS; Bloom SM; Norian LA; Geske MJ; Flavell RA; Stappenbeck TS; Allen PM. 2008. An antibiotic-responsive mouse model of fulminant ulcerative colitis. PLoS Med 5(3):e41. [PubMed: 18318596]  [MGI Ref ID J:134156]

Khare A; Krishnamoorthy N; Oriss TB; Fei M; Ray P; Ray A. 2013. Cutting edge: inhaled antigen upregulates retinaldehyde dehydrogenase in lung CD103+ but not plasmacytoid dendritic cells to induce Foxp3 de novo in CD4+ T cells and promote airway tolerance. J Immunol 191(1):25-9. [PubMed: 23733880]  [MGI Ref ID J:205351]

Kretschmer K; Apostolou I; Hawiger D; Khazaie K; Nussenzweig MC; von Boehmer H. 2005. Inducing and expanding regulatory T cell populations by foreign antigen. Nat Immunol 6(12):1219-27. [PubMed: 16244650]  [MGI Ref ID J:112677]

Lathrop SK; Bloom SM; Rao SM; Nutsch K; Lio CW; Santacruz N; Peterson DA; Stappenbeck TS; Hsieh CS. 2011. Peripheral education of the immune system by colonic commensal microbiota. Nature 478(7368):250-4. [PubMed: 21937990]  [MGI Ref ID J:177128]

Lee JH; Wang C; Kim CH. 2009. FoxP3+ regulatory T cells restrain splenic extramedullary myelopoiesis via suppression of hemopoietic cytokine-producing T cells. J Immunol 183(10):6377-86. [PubMed: 19890066]  [MGI Ref ID J:157163]

Lee YT; Suarez-Ramirez JE; Wu T; Redman JM; Bouchard K; Hadley GA; Cauley LS. 2011. Environmental and antigen receptor-derived signals support sustained surveillance of the lungs by pathogen-specific cytotoxic T lymphocytes. J Virol 85(9):4085-94. [PubMed: 21345961]  [MGI Ref ID J:173855]

Liu G; Yang K; Burns S; Shrestha S; Chi H. 2010. The S1P(1)-mTOR axis directs the reciprocal differentiation of T(H)1 and T(reg) cells. Nat Immunol 11(11):1047-56. [PubMed: 20852647]  [MGI Ref ID J:166555]

Monteiro M; Almeida CF; Caridade M; Ribot JC; Duarte J; Agua-Doce A; Wollenberg I; Silva-Santos B; Graca L. 2010. Identification of Regulatory Foxp3+ Invariant NKT Cells Induced by TGF-{beta}. J Immunol 185(4):2157-63. [PubMed: 20639482]  [MGI Ref ID J:162545]

Moritoki Y; Zhang W; Tsuneyama K; Yoshida K; Wakabayashi K; Yang GX; Bowlus C; Ridgway WM; Ueno Y; Ansari AA; Coppel RL; Mackay IR; Flavell RA; Gershwin ME; Lian ZX. 2009. B cells suppress the inflammatory response in a mouse model of primary biliary cirrhosis. Gastroenterology 136(3):1037-47. [PubMed: 19118554]  [MGI Ref ID J:146916]

Oertelt S; Lian ZX; Cheng CM; Chuang YH; Padgett KA; He XS; Ridgway WM; Ansari AA; Coppel RL; Li MO; Flavell RA; Kronenberg M; Mackay IR; Gershwin ME. 2006. Anti-mitochondrial antibodies and primary biliary cirrhosis in TGF-beta receptor II dominant-negative mice. J Immunol 177(3):1655-60. [PubMed: 16849474]  [MGI Ref ID J:138001]

Pu H; Collazo J; Jones E; Gayheart D; Sakamoto S; Vogt A; Mitchell B; Kyprianou N. 2009. Dysfunctional transforming growth factor-beta receptor II accelerates prostate tumorigenesis in the TRAMP mouse model. Cancer Res 69(18):7366-74. [PubMed: 19738062]  [MGI Ref ID J:152684]

Qin H; Wang L; Feng T; Elson CO; Niyongere SA; Lee SJ; Reynolds SL; Weaver CT; Roarty K; Serra R; Benveniste EN; Cong Y. 2009. TGF-{beta} Promotes Th17 Cell Development through Inhibition of SOCS3. J Immunol 183(1):97-105. [PubMed: 19535626]  [MGI Ref ID J:150117]

Quintana FJ; Basso AS; Iglesias AH; Korn T; Farez MF; Bettelli E; Caccamo M; Oukka M; Weiner HL. 2008. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453(7191):65-71. [PubMed: 18362915]  [MGI Ref ID J:136052]

Reardon C; Duncan GS; Brustle A; Brenner D; Tusche MW; Olofsson P; Rosas-Ballina M; Tracey KJ; Mak TW. 2013. Lymphocyte-derived ACh regulates local innate but not adaptive immunity. Proc Natl Acad Sci U S A 110(4):1410-5. [PubMed: 23297238]  [MGI Ref ID J:193708]

Regateiro FS; Chen Y; Kendal AR; Hilbrands R; Adams E; Cobbold SP; Ma J; Andersen KG; Betz AG; Zhang M; Madhiwalla S; Roberts B; Waldmann H; Nolan KF; Howie D. 2012. Foxp3 expression is required for the induction of therapeutic tissue tolerance. J Immunol 189(8):3947-56. [PubMed: 22988034]  [MGI Ref ID J:190639]

Reynolds LA; Maizels RM. 2012. Cutting edge: in the absence of TGF-beta signaling in T cells, fewer CD103+ regulatory T cells develop, but exuberant IFN-gamma production renders mice more susceptible to helminth infection. J Immunol 189(3):1113-7. [PubMed: 22753928]  [MGI Ref ID J:189778]

Sanjabi S; Mosaheb MM; Flavell RA. 2009. Opposing effects of TGF-beta and IL-15 cytokines control the number of short-lived effector CD8+ T cells. Immunity 31(1):131-44. [PubMed: 19604492]  [MGI Ref ID J:151577]

Schallenberg S; Tsai PY; Riewaldt J; Kretschmer K. 2010. Identification of an immediate Foxp3(-) precursor to Foxp3(+) regulatory T cells in peripheral lymphoid organs of nonmanipulated mice. J Exp Med 207(7):1393-407. [PubMed: 20584884]  [MGI Ref ID J:163388]

Takami M; Love RB; Iwashima M. 2012. TGF-beta converts apoptotic stimuli into the signal for Th9 differentiation. J Immunol 188(9):4369-75. [PubMed: 22461692]  [MGI Ref ID J:188456]

Tanaka H; Yang GX; Iwakoshi N; Knechtle SJ; Kawata K; Tsuneyama K; Leung P; Coppel RL; Ansari AA; Joh T; Bowlus C; Gershwin ME. 2013. Anti-CD40 ligand monoclonal antibody delays the progression of murine autoimmune cholangitis. Clin Exp Immunol 174(3):364-71. [PubMed: 23981074]  [MGI Ref ID J:202340]

Tinoco R; Alcalde V; Yang Y; Sauer K; Zuniga EI. 2009. Cell-intrinsic transforming growth factor-beta signaling mediates virus-specific CD8+ T cell deletion and viral persistence in vivo. Immunity 31(1):145-57. [PubMed: 19604493]  [MGI Ref ID J:151576]

Veldhoen M; Hocking RJ; Flavell RA; Stockinger B. 2006. Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nat Immunol 7(11):1151-6. [PubMed: 16998492]  [MGI Ref ID J:113559]

Veldhoen M; Uyttenhove C; van Snick J; Helmby H; Westendorf A; Buer J; Martin B; Wilhelm C; Stockinger B. 2008. Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 9(12):1341-6. [PubMed: 18931678]  [MGI Ref ID J:143562]

Wang C; Kang SG; Lee J; Sun Z; Kim CH. 2009. The roles of CCR6 in migration of Th17 cells and regulation of effector T-cell balance in the gut. Mucosal Immunol 2(2):173-83. [PubMed: 19129757]  [MGI Ref ID J:191919]

Wei HX; Chuang YH; Li B; Wei H; Sun R; Moritoki Y; Gershwin ME; Lian ZX; Tian Z. 2008. CD4+ CD25+ Foxp3+ regulatory T cells protect against T cell-mediated fulminant hepatitis in a TGF-beta-dependent manner in mice. J Immunol 181(10):7221-9. [PubMed: 18981144]  [MGI Ref ID J:141078]

Wohlfert EA; Gorelik L; Mittler R; Flavell RA; Clark RB. 2006. Cutting edge: deficiency in the E3 ubiquitin ligase Cbl-b results in a multifunctional defect in T cell TGF-beta sensitivity in vitro and in vivo. J Immunol 176(3):1316-20. [PubMed: 16424156]  [MGI Ref ID J:126434]

Yang CY; Leung PS; Yang GX; Kenny TP; Zhang W; Coppel R; Norman GL; Ansari AA; Mackay IR; Worman HJ; Gershwin ME. 2012. Epitope-specific anti-nuclear antibodies are expressed in a mouse model of primary biliary cirrhosis and are cytokine-dependent. Clin Exp Immunol 168(3):261-7. [PubMed: 22519587]  [MGI Ref ID J:184866]

Zhang W; Tsuda M; Yang GX; Tsuneyama K; He XS; Ansari AA; Ridgway WM; Coppel RL; Lian ZX; Leung PS; Gershwin ME. 2012. Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFbeta receptor II. PLoS One 7(11):e49413. [PubMed: 23145171]  [MGI Ref ID J:194795]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as hemizygotes. The Donating Investigator recommends either using only male mice for breeding or fostering pups as hemizygous female mice do not support pregnancies well. These transgenic mice have a reduced lifespan due to autoimmune disease. The Donating Investigator recommends prophylactic antibiotic treatment (for example, Sulfatrim).
Mating SystemInbred x Hemizygote         (Female x Male)   27-JUN-06
Diet Information LabDiet® 5K52/5K67

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 $239.00Female or MaleHemizygous for Tg(Cd4-TGFBR2)16Flv  
Price per Pair (US dollars $)Pair Genotype
$261.55C57BL/6J (000664) x Hemizygous for Tg(Cd4-TGFBR2)16Flv  

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 $310.70Female or MaleHemizygous for Tg(Cd4-TGFBR2)16Flv  
Price per Pair (US dollars $)Pair Genotype
$340.10C57BL/6J (000664) x Hemizygous for Tg(Cd4-TGFBR2)16Flv  

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

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


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 Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"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.

No Warranty

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 mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

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 and PRODUCTS 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.


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