Strain Name:

NOD/ShiLtDvs-Tg(HLA-A/H2-D/B2M)1Dvs/J

Stock Number:

006604

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Availability:

Cryopreserved - Ready for recovery

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.
Specieslaboratory mouse
Background Strain NOD/ShiLtJ
Donor Strain NOD/ShiLtDvs
H2 Haplotypeg7
GenerationN1F15pN1
Generation Definitions
 
Donating InvestigatorDr. David Serreze,   The Jackson Laboratory

Appearance
albino, pink eyed
Related Genotype: A/A Tyrc/Tyrc

Description
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

View Strains carrying   Tg(HLA-A/H2-D/B2M)1Dvs     (3 strains)

View Strains carrying other alleles of B2M     (8 strains)

View Strains carrying other alleles of HLA-A     (9 strains)

View Strains carrying other alleles of HLA-A2.1     (8 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- 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)
Severe Cutaneous Adverse Reaction, Susceptibility to   (HLA-A)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      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)
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
      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 (Inserted expressed sequence)
Common Name(s) HDD; HHD;
Mutation Made ByDr. David Serreze,   The Jackson Laboratory
Strain of OriginNOD/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 related

Chen X; Tang Y; Zhang Y; Zhuo M; Tang Z; Yu Y; Zang G. 2014. Tapasin modification on the intracellular epitope HBcAg18-27 enhances HBV-specific CTL immune response and inhibits hepatitis B virus replication in vivo. Lab Invest 94(5):478-90. [PubMed: 24614195]  [MGI Ref ID J:208402]

Enee 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 View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
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 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* $2782.00
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 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
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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