| 
| ||||||||||||||
- 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
Former Names NOD/ShiLtDvs-Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ (Changed: 06-JUN-07 ) NOD/Lt-Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ (Changed: 06-JUN-07 ) Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Background Strain NOD/ShiLtJ Donor Strain NOD/ShiLtDvs H2 Haplotype g7 Generation N1F15pN1
Generation DefinitionsDonating Investigator Dr. David Serreze, The Jackson Laboratory Appearance
albino, pink eyed
Related Genotype: A/A Tyrc/TyrcDescription
This transgenic NOD mouse model, commonly referred to as NOD.HHD, develops significantly accelerated diabetes onset compared to NOD/ShiLtDvs (NOD) inbred mice.When transgenic mice are bred to NOD-B2m-deficient mice (e.g. Stock No. 002309), which completely lack CD8+ T cells, CD8+ T cells are restored in the double mutant mice, but at significantly lower levels than in NOD inbred mice. FACS analysis indicates that the transgenic NOD-B2m-deficient mice express only the HLA-A2.1/H2-Db chimeric class I molecule. In contrast to NOD.B2mtm1Unc females, which are diabetes free, 55% of the transgenic NOD B2m-deficient females develop diabetes by 30 weeks of age. Insulitis scores determined by histological examination are similar between the NOD double mutant mice and NOD/ShiLtDvs inbred mice, and cultured pancreatic islets from transgenic NOD B2m-deficient mice and from NOD inbred mice produce comparable numbers of CD8+ T cells. Further, the T cells isolated from the transgenic NOD B2m-deficient-derived islet cultures are HLA-A2.1 specific, and are able to recognize islet-specific antigens, such as the Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP).
NOD transgenic mice carrying the Prkdcscid (Stock No. 006605) do not become diabetic.
This model provides humanized T cells that will be a useful tool to identify MHC class I epitopes recognized by CD8+ T cells in type 1 diabetes patients and for testing new therapies focusing on restoring immune tolerance.
Development
This transgene encodes a human B2-microglubulin (B2M) covalently linked to the MHC class 1, alpha1 and alpha2 binding domains of the human HLA-A2.1 gene and the alpha3, cytoplasmic and transmembrane domains of the murine H2-Db. The transgene was injected into NOD/ShiLtDvs embryos. In 2007, the T1DR received this stock at N1F15. The T1DR mated to NOD/ShiLtJ once prior to sibling mating.
Control Information
| Control | ||
|---|---|---|
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Tg(HLA-A/H2-D/B2M)1Dvs allele
006611 NOD.129P2(B6)-B2mtm1Unc Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ 006605 NOD.Cg-Prkdcscid Emv30b Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ 014570 NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(HLA-A/H2-D/B2M)1Dvs/SzJ View Strains carrying Tg(HLA-A/H2-D/B2M)1Dvs (3 strains)
Phenotype
Phenotype Information
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Diabetes Mellitus, Insulin-Dependent; IDDM
- 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. Hypoproteinemia, Hypercatabolic (B2M)
Major Histocompatibility Complex, Class I, A; HLA-A (HLA-A)
Severe Cutaneous Adverse Reaction, Susceptibility to (HLA-A)
assigned by genotype
Tg(HLA-A/H2-D/B2M)1Dvs/0
NOD/ShiLtDvs-Tg(HLA-A/H2-D/B2M)1Dvs
- immune system phenotype
- increased susceptibility to autoimmune diabetes
- females develop accelerated type I diabetes through 30 weeks of age, compared to NOD controls (MGI Ref ID J:121685)
This mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains
NOD Transgenics
Immunology, Inflammation and Autoimmunity Research
Autoimmunity
Type 1 Diabetes
CD Antigens, Antigen Receptors, and Histocompatibility Markers
HLA transgenics
Vaccine Development
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(HLA-A/H2-D/B2M)1Dvs | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, David Serreze | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | HDD; HHD; | ||
| Mutation Made By | Dr. David Serreze, The Jackson Laboratory | ||
| Strain of Origin | NOD/ShiLtDvs | ||
| Expressed Gene | B2M, beta-2-microglobulin, human | ||
| Expressed Gene | HLA-A, major histocompatibility complex, class I, A, human | ||
| Promoter | HLA-A2.1, major histocompatibility complex, class I, subtype A2.1, human | ||
| General Note | The HDD construct was created and used to generate a differnet transgenic mouse line in J:41077. | ||
| Molecular Note | This transgene encodes a human B2-microglubulin (B2M) covalently linked to the MHC class 1, alpha1 and alpha2 binding domains of the human HLA-A2.1 gene, and the alpha3, cytoplasmic and transmembrane domains of the murine H2-Db. The constructwas injected into fertilized NOD/ShiLtDvs oocytes. The construct was originally described in J:41077 and used to create a different transgenic line. [MGI Ref ID J:121685] [MGI Ref ID J:41077] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(HLA-A/H2-D), QPCR
Tg(HLA-A/H2-D), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Pascolo S; Bervas N; Ure JM; Smith AG; Lemonnier FA; Perarnau B. 1997. HLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice. J Exp Med 185(12):2043-51. [PubMed: 9182675] [MGI Ref ID J:41077]
Takaki T; Marron MP; Mathews CE; Guttmann ST; Bottino R; Trucco M; DiLorenzo TP; Serreze DV. 2006. HLA-A*0201-restricted T cells from humanized NOD mice recognize autoantigens of potential clinical relevance to type 1 diabetes. J Immunol 176(5):3257-65. [PubMed: 16493087] [MGI Ref ID J:121685]
Additional References
Tg(HLA-A/H2-D/B2M)1Dvs relatedEnee E; Martinuzzi E; Blancou P; Bach JM; Mallone R; van Endert P. 2008. Equivalent specificity of peripheral blood and islet-infiltrating CD8+ T lymphocytes in spontaneously diabetic HLA-A2 transgenic NOD mice. J Immunol 180(8):5430-8. [PubMed: 18390725] [MGI Ref ID J:134255]
Jaiswal S; Pearson T; Friberg H; Shultz LD; Greiner DL; Rothman AL; Mathew A. 2009. Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rgammanull mice. PLoS One 4(10):e7251. [PubMed: 19802382] [MGI Ref ID J:154110]
Jarchum I; Baker JC; Yamada T; Takaki T; Marron MP; Serreze DV; DiLorenzo TP. 2007. In vivo cytotoxicity of insulin-specific CD8+ T-cells in HLA-A*0201 transgenic NOD mice. Diabetes 56(10):2551-60. [PubMed: 17620420] [MGI Ref ID J:126569]
Jarchum I; DiLorenzo TP. 2010. Ins2 deficiency augments spontaneous HLA-A*0201-restricted T cell responses to insulin. J Immunol 184(2):658-65. [PubMed: 19966211] [MGI Ref ID J:159429]
Niens M; Grier AE; Marron M; Kay TW; Greiner DL; Serreze DV. 2011. Prevention of 'Humanized' diabetogenic CD8 T-cell responses in HLA-transgenic NOD mice by a multipeptide coupled-cell approach. Diabetes 60(4):1229-36. [PubMed: 21346176] [MGI Ref ID J:171756]
Serreze DV; Marron MP; Dilorenzo TP. 2007. 'Humanized' HLA transgenic NOD mice to identify pancreatic beta cell autoantigens of potential clinical relevance to type 1 diabetes. Ann N Y Acad Sci 1103:103-11. [PubMed: 17376821] [MGI Ref ID J:123948]
Shultz LD; Saito Y; Najima Y; Tanaka S; Ochi T; Tomizawa M; Doi T; Sone A; Suzuki N; Fujiwara H; Yasukawa M; Ishikawa F. 2010. Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r gamma(null) humanized mice. Proc Natl Acad Sci U S A 107(29):13022-7. [PubMed: 20615947] [MGI Ref ID J:162315]
Tsai S; Shameli A; Yamanouchi J; Clemente-Casares X; Wang J; Serra P; Yang Y; Medarova Z; Moore A; Santamaria P. 2010. Reversal of autoimmunity by boosting memory-like autoregulatory T cells. Immunity 32(4):568-80. [PubMed: 20381385] [MGI Ref ID J:179859]
Whitfield-Larry F; Young EF; Talmage G; Fudge E; Azam A; Patel S; Largay J; Byrd W; Buse J; Calikoglu AS; Shultz LD; Frelinger JA. 2011. HLA-A2-matched peripheral blood mononuclear cells from type 1 diabetic patients, but not nondiabetic donors, transfer insulitis to NOD-scid/gammac(null)/HLA-A2 transgenic mice concurrent with the expansion of islet-specific CD8+ T cells. Diabetes 60(6):1726-33. [PubMed: 21521873] [MGI Ref ID J:177952]
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* $1980.00 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* $2574.00 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.
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| 001976 NOD/ShiLtJ | ||
| 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.