Strain Name:

NOD.129S4(B6)-Art2atm1Fkn Art2btm1Fkn/LtJ

Stock Number:

008252

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Availability:

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Common Names: NOD.Art2;    
This Art2a and Art2b targeted mutant strain becomes diabetic at a similar onset and rate as NOD/ShiLt mice. The absence of ART2 expression on T cells from thymus and lymph nodes was confirmed by RT-PCR and FACS analysis. Cd4+ and CD8+ T cells from ART2 deficient NOD mice are completely resistant to NAD induced apoptosis at all concentrations in vitro. This ART2 deficient stock provides a tool to further dissect the interplay of ADP rybosylation and NAD-catabolizing enzymes and their effect on Tregs and iNKT involved in autoimmune diseases specifically, Type 1 Diabetes.

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; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Background Strain NOD/ShiLt
Donor Strain B6.129S4
H2 Haplotypeg7
GenerationN11F17p
Generation Definitions
 
Donating InvestigatorDr. Edward Leiter,   The Jackson Laboratory

Description
Art2a, Art2b, commonly referred to as ART2, deficient mice are viable and fertile and do not show any overt phenotype. RT-PCR and FACS analysis confirm the absence of ART2 expression on the cell surface of thymic and lymph node purified T cells. No detectable histological abnormalities were observed in the thymus, spleens, lymph nodes, Peyer's patches, thyroid, brain, lung, kidney, intestine, liver, pancreas and thyroid. The disrupted introgression of ART2 onto the NOD background resulted in no significant difference in diabetes onset or incidence when compared to NOD. When the Cd38 targeted mutation is introduced to the NOD.ART2 deficient stock, the NOD.CD38, ART2 deficient males and females are completely resistant to diabetes. This is a surprising result as the NOD.CD38 deficient stock experiences accelerated diabetes onset and incidence in both males and females. Cd4+ and CD8+ T cells from ART2 deficient NOD mice are completely resistant to NAD induced apoptosis at all concentrations in vitro.

The ART2 targeted mutation provides a tool to further dissect the interplay of ADP rybosylation and NAD-catabolizing enzymes and their effect on Tregs and iNKT involved in autoimmune diseases specifically, Type 1 Diabetes.

Development
Art2, ADP-ribosyltransferase 2, is a NAD-metabolizing ectoenzyme expressed on the surface of peripheral T cells and shed upon activation. The Art2a and Art2b genes were disrupted via homologous recombination in 129S4/SvJae-derived, J1 ES cells. Most of exon 3, the major coding exon, of Art2a was replaced with a neomycin resistance cassette. The ES cell clone bearing the Art2a targeted mutation was then transfected with a construct which replaced most of the major coding exon of Art2b with a hygromycin resistance cassette. The resulting ES cell clone with two targeted mutations was injected into blastocysts. The resulting chimeric founder's offspring were bred to C57BL/6J prior to 11 generations of crossing to NOD/ShiLt and intercrossing. In 2008, the T1DR received mice homozygous for the Art2a/Art2b mutation at generation N11F16.

Control Information

  Control
   001976 NOD/ShiLtJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Art2a-pstm1Fkn allele
005347   NOD.129(B6)-Cd38tm1Lnd Art2atm1Fkn Art2btm1Fkn/Lt
View Strains carrying   Art2a-pstm1Fkn     (1 strain)

Strains carrying   Art2btm1Fkn allele
005347   NOD.129(B6)-Cd38tm1Lnd Art2atm1Fkn Art2btm1Fkn/Lt
View Strains carrying   Art2btm1Fkn     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Art2a-pstm1Fkn/Art2a-pstm1Fkn Art2btm1Fkn/Art2btm1Fkn

        NOD.129S4(B6)-Art2atm1Fkn Art2btm1Fkn/Lt
  • immune system phenotype
  • decreased T cell apoptosis
    • CD4+ and CD8+ T cells are completely resistant to NAD-mediated apoptosis in Art2-deficient NOD mice compared to wild-type NOD mice which exhibit T cell apoptosis in a dose-dependent manner compared to Art2-intact NOD mice   (MGI Ref ID J:108097)
  • cellular phenotype
  • decreased T cell apoptosis
    • CD4+ and CD8+ T cells are completely resistant to NAD-mediated apoptosis in Art2-deficient NOD mice compared to wild-type NOD mice which exhibit T cell apoptosis in a dose-dependent manner compared to Art2-intact NOD mice   (MGI Ref ID J:108097)
  • hematopoietic system phenotype
  • decreased T cell apoptosis
    • CD4+ and CD8+ T cells are completely resistant to NAD-mediated apoptosis in Art2-deficient NOD mice compared to wild-type NOD mice which exhibit T cell apoptosis in a dose-dependent manner compared to Art2-intact NOD mice   (MGI Ref ID J:108097)
View Research Applications

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

Diabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
      Type 1 Diabetes

Research Tools
Immunology, Inflammation and Autoimmunity Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Art2a-pstm1Fkn
Allele Name targeted mutation 1, Friedrich Koch-Noltet
Allele Type Targeted (Null/Knockout)
Common Name(s) ART2.1-;
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Art2a-ps, ADP-ribosyltransferase 2a, pseudogene
Chromosome 7
Gene Common Name(s) Rt-6; Rt6; Rt6-1; rat homolog Rt6, locus 1; rat homolog of transplantable antigen gene RT6;
General Note Successfully targeted ES cells were subsequently targeted with the construct for the Art2b allele.
Molecular Note The coding region was disrupted by a neomycin selection cassette inserted by homologous recombination. Transcript was undetected in homozygous mutant mice by RT-PCR analysis of T cells isolated from lymph nodes. [MGI Ref ID J:79607]
 
Allele Symbol Art2btm1Fkn
Allele Name targeted mutation 1, Friedrich Koch-Nolte
Allele Type Targeted (Null/Knockout)
Common Name(s) ART2.2-;
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Art2b, ADP-ribosyltransferase 2b
Chromosome 7
Gene Common Name(s) ART2.2; ARTC2; Ag-F; Art2; Art2a; LY2; Ly-2; PtaA; RT6.1; RT6.2; Rt-6; Rt6; Rt6-2; homolog of rat transplantable antigen gene RT6; rat homolog Rt6, locus 2;
General Note The targeting vector was electroporated into J1 ES cells carrying Art2atm1Fkn.
Molecular Note The coding region was disrupted by a hygromycin selection cassette inserted by homologous recombination. This construct was used to transfect mice in which the Art2atm1Fkn allele had already been created Transcript was undetected in homozygousmutant mice by RT-PCR analysis of T cells isolated from lymph nodes. FACS analysis of thymocytes and lymphocytes indicated a lack of protein expression on the cell surface. [MGI Ref ID J:79607]

Genotyping

Genotyping Information

Genotyping Protocols

Art2atm1Fkn, Separated PCR
Art2btm1Fkn, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Chen J; Chen YG; Reifsnyder PC; Schott WH; Lee CH; Osborne M; Scheuplein F; Haag F; Koch-Nolte F; Serreze DV; Leiter EH. 2006. Targeted disruption of CD38 accelerates autoimmune diabetes in NOD/Lt mice by enhancing autoimmunity in an ADP-ribosyltransferase 2-dependent fashion. J Immunol 176(8):4590-9. [PubMed: 16585549]  [MGI Ref ID J:108097]

Chen YG; Chen J; Osborne MA; Chapman HD; Besra GS; Porcelli SA; Leiter EH; Wilson SB; Serreze DV. 2006. CD38 is required for the peripheral survival of immunotolerogenic CD4+ invariant NK T cells in nonobese diabetic mice. J Immunol 177(5):2939-47. [PubMed: 16920929]  [MGI Ref ID J:112615]

Additional References

Art2a-pstm1Fkn related

Adriouch S; Hubert S; Pechberty S; Koch-Nolte F; Haag F; Seman M. 2007. NAD+ released during inflammation participates in T cell homeostasis by inducing ART2-mediated death of naive T cells in vivo. J Immunol 179(1):186-94. [PubMed: 17579037]  [MGI Ref ID J:149420]

Chen YG; Scheuplein F; Driver JP; Hewes AA; Reifsnyder PC; Leiter EH; Serreze DV. 2011. Testing the Role of P2X7 Receptors in the Development of Type 1 Diabetes in Nonobese Diabetic Mice. J Immunol :. [PubMed: 21357538]  [MGI Ref ID J:169661]

Hubert S; Rissiek B; Klages K; Huehn J; Sparwasser T; Haag F; Koch-Nolte F; Boyer O; Seman M; Adriouch S. 2010. Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. J Exp Med 207(12):2561-8. [PubMed: 20975043]  [MGI Ref ID J:176876]

Kawamura H; Aswad F; Minagawa M; Govindarajan S; Dennert G. 2006. P2X7 receptors regulate NKT cells in autoimmune hepatitis. J Immunol 176(4):2152-60. [PubMed: 16455971]  [MGI Ref ID J:129123]

Krebs C; Adriouch S; Braasch F; Koestner W; Leiter EH; Seman M; Lund FE; Oppenheimer N; Haag F; Koch-Nolte F. 2005. CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins. J Immunol 174(6):3298-305. [PubMed: 15749861]  [MGI Ref ID J:97699]

Lischke T; Schumacher V; Wesolowski J; Hurwitz R; Haag F; Koch-Nolte F; Mittrucker HW. 2013. CD8-beta ADP-ribosylation affects CD8(+) T-cell function. Eur J Immunol 43(7):1828-38. [PubMed: 23575529]  [MGI Ref ID J:201025]

Ohlrogge W; Haag F; Lohler J; Seman M; Littman DR; Killeen N; Koch-Nolte F. 2002. Generation and characterization of ecto-ADP-ribosyltransferase ART2.1/ART2.2-deficient mice. Mol Cell Biol 22(21):7535-42. [PubMed: 12370300]  [MGI Ref ID J:79607]

Art2btm1Fkn related

Adriouch S; Hubert S; Pechberty S; Koch-Nolte F; Haag F; Seman M. 2007. NAD+ released during inflammation participates in T cell homeostasis by inducing ART2-mediated death of naive T cells in vivo. J Immunol 179(1):186-94. [PubMed: 17579037]  [MGI Ref ID J:149420]

Bannas P; Scheuplein F; Well L; Hermans-Borgmeyer I; Haag F; Koch-Nolte F. 2011. Transgenic overexpression of toxin-related ecto-ADP-ribosyltransferase ART2.2 sensitizes T cells but not B cells to NAD-induced cell death. Mol Immunol 48(15-16):1762-70. [PubMed: 21641039]  [MGI Ref ID J:177223]

Chen YG; Scheuplein F; Driver JP; Hewes AA; Reifsnyder PC; Leiter EH; Serreze DV. 2011. Testing the Role of P2X7 Receptors in the Development of Type 1 Diabetes in Nonobese Diabetic Mice. J Immunol :. [PubMed: 21357538]  [MGI Ref ID J:169661]

Heiss K; Janner N; Mahnss B; Schumacher V; Koch-Nolte F; Haag F; Mittrucker HW. 2008. High sensitivity of intestinal CD8+ T cells to nucleotides indicates P2X7 as a regulator for intestinal T cell responses. J Immunol 181(6):3861-9. [PubMed: 18768840]  [MGI Ref ID J:139109]

Hubert S; Rissiek B; Klages K; Huehn J; Sparwasser T; Haag F; Koch-Nolte F; Boyer O; Seman M; Adriouch S. 2010. Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. J Exp Med 207(12):2561-8. [PubMed: 20975043]  [MGI Ref ID J:176876]

Kawamura H; Aswad F; Minagawa M; Govindarajan S; Dennert G. 2006. P2X7 receptors regulate NKT cells in autoimmune hepatitis. J Immunol 176(4):2152-60. [PubMed: 16455971]  [MGI Ref ID J:129123]

Krebs C; Adriouch S; Braasch F; Koestner W; Leiter EH; Seman M; Lund FE; Oppenheimer N; Haag F; Koch-Nolte F. 2005. CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins. J Immunol 174(6):3298-305. [PubMed: 15749861]  [MGI Ref ID J:97699]

Lischke T; Schumacher V; Wesolowski J; Hurwitz R; Haag F; Koch-Nolte F; Mittrucker HW. 2013. CD8-beta ADP-ribosylation affects CD8(+) T-cell function. Eur J Immunol 43(7):1828-38. [PubMed: 23575529]  [MGI Ref ID J:201025]

Ohlrogge W; Haag F; Lohler J; Seman M; Littman DR; Killeen N; Koch-Nolte F. 2002. Generation and characterization of ecto-ADP-ribosyltransferase ART2.1/ART2.2-deficient mice. Mol Cell Biol 22(21):7535-42. [PubMed: 12370300]  [MGI Ref ID J:79607]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

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* $2525.00
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 willfulfill 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 10 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* $3283.00
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 willfulfill 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 10 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.

General Supply Notes

Control Information

  Control
   001976 NOD/ShiLtJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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