| 
| |||||||||||||||||
| 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
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
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. Species laboratory mouse Background Strain NOD/ShiLt Donor Strain B6.129S4 H2 Haplotype g7 Generation N11F17p
Generation DefinitionsDonating Investigator Dr. 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)
005347 NOD.129(B6)-Cd38tm1Lnd Art2atm1Fkn Art2btm1Fkn/Lt
Phenotype
Phenotype Information
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)
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 and Inflammation Research
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Art2a-pstm1Fkn | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Friedrich Koch-Noltet | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | ART2.1-; | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/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 | ||
| 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 (knock-out) | ||
| Common Name(s) | ART2.2-; | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/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 relatedArt2btm1Fkn relatedAdriouch 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]
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]
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]
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 |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 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 |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 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).
|
|
|
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- This strain is included in the Type 1 Diabetes Repository collection.
Control Information
| Control | ||
|---|---|---|
| 001976 NOD/ShiLtJ | (approximate) | |
| 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
Contact information
General inquiries regarding Terms of UseContracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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.