Strain Name:

B6.Cg-Tg(Itgax-TGFBR2)1Flv/J

Stock Number:

008378

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Cryopreserved - Ready for recovery

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These CD11c-dnTGFbRIII transgenic mice express a dominant negative form of the human transforming growth factor, beta receptor II gene under the control of a CD11c (Itgax) promoter. Expression of the transgene is detected by RT-PCR in CD11c-expressing cells, including natural killer (NK) cell and lymphoid/myeloid dendritic cell (DC) subsets. Expression is not detected in natural killer T cells (NKT) cells, T cells or B cells isolated from transgenic mice. Transgenic mice show a selective dysregulation of NK cell homeostasis due to a blockage of transforming growth factor, beta (Tgfb) signalling. Large numbers of NK cells capable of producing considerable levels of interferon gamma (IFN-g) lead to downstream T helper type 1 (TH1) cell polarization.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN?pN1
Generation Definitions
 
Donating InvestigatorDr. Richard A. Flavell,   Yale University School of Medicine

Description
These CD11c-dnTGFβRII transgenic mice express a dominant negative form of the human transforming growth factor, beta receptor II gene under the control of a CD11c (Itgax) promoter. This form of the receptor blocks transforming growth factor, beta (Tgfb) signalling when its expression is sufficiently high to interfere with the assembly of a functional signaling complex consisting of transforming growth factor beta and type II and type I transforming growth factor beta receptors. Expression of the transgene is detected by RT-PCR in CD11c-expressing cells, including natural killer (NK) cell and lymphoid/myeloid dendritic cell (DC) subsets. Expression is not detected in natural killer T cells (NKT) cells, T cells or B cells isolated from transgenic mice. Transgenic mice show a selective dysregulation of NK cell homeostasis due to the blockage of transforming growth factor, beta (Tgfb) signalling. Large numbers of NK cells capable of producing considerable levels of interferon gamma (IFN-g) lead to downstream T helper type 1 (TH1) cell polarization. Mice bearing this transgene are viable and fertile and show no abnormalities in development.

Development
A transgenic vector carrying a CD11c (Itgax) mouse promoter driving the human dnTGFBRIII (Tgfbr2 transforming growth factor, beta receptor II) gene inserted into exon 3 of the rabbit beta globin gene was injected into (C57BL/6 x C3H)F1 hybrid fertilized eggs. The donating investigator reports that this line has been backcrossed more than 10 times to C57BL/6Ncr (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, at least 3 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

View Strains carrying other alleles of Itgax     (11 strains)

Strains carrying other alleles of TGFBR2
005551   B6.Cg-Tg(Cd4-TGFBR2)16Flv/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, Type 1B; LDS1B   (TGFBR2)
Loeys-Dietz Syndrome, Type 2B; LDS2B   (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(Itgax-TGFBR2)1Flv/0

        C.Cg-Tg(Itgax-TGFBR2)1Flv
  • immune system phenotype
  • *normal* immune system phenotype
    • size of dendritic cell (DC) compartment is normal in transgenic mice   (MGI Ref ID J:98953)
    • Flt3L treatment produces similar expansion of the DC compartment in mutants and controls   (MGI Ref ID J:98953)
    • abnormal NK cell differentiation
      • natural killer (NK) cell homeostasis is dysregulated, with transgenic mice showing a higher frequency (10%) of NK cells in spleen vs controls (frequency = 3%)   (MGI Ref ID J:98953)
      • higher frequencies of NK cells are found in other organs, including liver and bone marrow, compared to controls   (MGI Ref ID J:98953)
      • Flt3L induces a large degree of expansion of the NK cell compartment in transgenic mice relative to wild-type controls (20% vs 5%)   (MGI Ref ID J:98953)
      • in the presence of Il-15, transgenic splenocytes cultures show a 4-fold higher frequency of NK cells than cultured wild-type cells   (MGI Ref ID J:98953)
      • Tgfb (transforming growth factor beta) suppresses NK cell differentiation into Ifng-expressing cells in controls but has no effect in transgenic NK cells   (MGI Ref ID J:98953)
    • abnormal immune system physiology
      • transgenic T lymphocytes isolated from draining lymph nodes of Leishmania infection exhibit a strong TH1 response by differentiation into Ifng-expressing CD4+ T cells, while control cells show a strong TH2 response without Ifng production   (MGI Ref ID J:98953)
      • abnormal interferon level
        • transgenic NK cells have 4-5 fold higher Ifng (interferon gamma) levels than control cells upon stimulation by different doses of Il-12; NK cells have higher intracellular Ifng levels after infection compared to control NK cells   (MGI Ref ID J:98953)
        • expression of Ifng is high and sustained in NK cells from transgenic mice   (MGI Ref ID J:98953)
      • decreased susceptibility to parasitic infection
        • mice have increased resistance to infection by Leishmania major compared to wild-type controls   (MGI Ref ID J:98953)
    • increased NK cell number
      • by 3 weeks of age, mice 4-fold higher numbers of NK cells than controls; this is sustained throughout adult life; frequency of NK cells plateaus at 2 months of age   (MGI Ref ID J:98953)
  • hematopoietic system phenotype
  • abnormal NK cell differentiation
    • natural killer (NK) cell homeostasis is dysregulated, with transgenic mice showing a higher frequency (10%) of NK cells in spleen vs controls (frequency = 3%)   (MGI Ref ID J:98953)
    • higher frequencies of NK cells are found in other organs, including liver and bone marrow, compared to controls   (MGI Ref ID J:98953)
    • Flt3L induces a large degree of expansion of the NK cell compartment in transgenic mice relative to wild-type controls (20% vs 5%)   (MGI Ref ID J:98953)
    • in the presence of Il-15, transgenic splenocytes cultures show a 4-fold higher frequency of NK cells than cultured wild-type cells   (MGI Ref ID J:98953)
    • Tgfb (transforming growth factor beta) suppresses NK cell differentiation into Ifng-expressing cells in controls but has no effect in transgenic NK cells   (MGI Ref ID J:98953)
  • increased NK cell number
    • by 3 weeks of age, mice 4-fold higher numbers of NK cells than controls; this is sustained throughout adult life; frequency of NK cells plateaus at 2 months of age   (MGI Ref ID J:98953)
  • homeostasis/metabolism phenotype
  • abnormal interferon level
    • transgenic NK cells have 4-5 fold higher Ifng (interferon gamma) levels than control cells upon stimulation by different doses of Il-12; NK cells have higher intracellular Ifng levels after infection compared to control NK cells   (MGI Ref ID J:98953)
    • expression of Ifng is high and sustained in NK cells from transgenic mice   (MGI Ref ID J:98953)
View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Itgax-TGFBR2)1Flv
Allele Name transgene insertion 1, Richard A Flavell
Allele Type Transgenic (random, expressed)
Common Name(s) CD11c-dnTGFBRII; CD11cdnR; Cd11cdnTGFBR2;
Mutation Made ByDr. Richard Flavell,   Yale University School of Medicine
Strain of Origin(C57BL/6 x C3H)F1
Expressed Gene TGFBR2, transforming growth factor, beta receptor II (70/80kDa), human
Promoter Itgax, integrin alpha X, mouse, laboratory
Molecular Note The human TGFBRIII (Tgfbr2 transforming growth factor, beta receptor II) gene sequence between nucleotides -7 to +573 encoding the extracellular and transmembrane regions of TGFBR2 (dominant negative, dnTGFBR2) was inserted into exon 3 of the rabbit betaglobin gene in the plasmid Itgax promoter vector pDOI-5. The construct was injected into (C57BL/6 x C3H)F1 hybrid fertilized eggs. RT-PCR confirmed expression of dnTGFBR2 in Itgax (CD11c)-expressing cells including subsets of natural killer cell (NK) anddendritic cell (DC) subsets. No expression is detected in NKT cells, T cells or B cells. Expression is sufficient to block TFG beta signaling through the functional receptor exclusively in DCs and NK cells. [MGI Ref ID J:98953]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Itgax-TGFBR2), Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Laouar Y; Sutterwala FS; Gorelik L; Flavell RA. 2005. Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma. Nat Immunol 6(6):600-7. [PubMed: 15852008]  [MGI Ref ID J:98953]

Additional References

Tg(Itgax-TGFBR2)1Flv 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]

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]

Domingo-Gonzalez R; Huang SK; Laouar Y; Wilke CA; Moore BB. 2012. COX-2 expression is upregulated by DNA hypomethylation after hematopoietic stem cell transplantation. J Immunol 189(9):4528-36. [PubMed: 23008450]  [MGI Ref ID J:190616]

Hanks BA; Holtzhausen A; Evans KS; Jamieson R; Gimpel P; Campbell OM; Hector-Greene M; Sun L; Tewari A; George A; Starr M; Nixon A; Augustine C; Beasley G; Tyler DS; Osada T; Morse MA; Ling L; Lyerly HK; Blobe GC. 2013. Type III TGF-beta receptor downregulation generates an immunotolerant tumor microenvironment. J Clin Invest 123(9):3925-40. [PubMed: 23925295]  [MGI Ref ID J:201617]

Laouar Y; Town T; Jeng D; Tran E; Wan Y; Kuchroo VK; Flavell RA. 2008. TGF-beta signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 105(31):10865-70. [PubMed: 18669656]  [MGI Ref ID J:140054]

Marcoe JP; Lim JR; Schaubert KL; Fodil-Cornu N; Matka M; McCubbrey AL; Farr AR; Vidal SM; Laouar Y. 2012. TGF-beta is responsible for NK cell immaturity during ontogeny and increased susceptibility to infection during mouse infancy. Nat Immunol 13(9):843-50. [PubMed: 22863752]  [MGI Ref ID J:187587]

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]

Town T; Laouar Y; Pittenger C; Mori T; Szekely CA; Tan J; Duman RS; Flavell RA. 2008. Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat Med 14(6):681-7. [PubMed: 18516051]  [MGI Ref ID J:137043]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, hemizygotes may be bred with wildtype mice.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3175.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $4127.50
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Noncarrier
   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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