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
Donating Investigator Dr. David Serreze, The Jackson Laboratory
albino, pink eyed
Related Genotype: A/A Tyrc/Tyrc
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.
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.
|Considerations for Choosing Controls|
Strains carrying Tg(HLA-A/H2-D/B2M)1Dvs alleleView Strains carrying Tg(HLA-A/H2-D/B2M)1Dvs (3 strains)Strains carrying other alleles of B2M
003428 B6(Cg)-Tg(B2M)1Trg Tg(HLA-B)1Trg/Dcr 008337 CBA/Ca-Tg(H2-K-HLA-G,B2M)1Alm/CmwJ 010565 NOD.129P2(B6)-B2mtm1Unc Tg(HLA-A24/H2-D/B2M)3Dvs/J 003355 NOD.Cg-B2mtm1Unc Tg(B2M)55Hpl/Dvs 004548 NOD.Cg-B2mtm1Unc Tg(B2M)55Hpl Tg(HLA-A2.1)1Enge/DvsJ 018907 NOD.Cg-B2mtm1Unc Tg(B2M)55Hpl Tg(HLA-B*0702)#Chmb/TdilJ 004342 NOD.Cg-Tg(B2M)1Trg Tg(HLA-B)1Trg/Dvs 003356 NOD.Cg-Tg(B2M)55Hpl/DvsView Strains carrying other alleles of B2M (8 strains)Strains carrying other alleles of HLA-A
004191 B6.Cg-Tg(HLA-A/H2-D)2Enge/J 003475 C57BL/6-Tg(HLA-A2.1)1Enge/J 010565 NOD.129P2(B6)-B2mtm1Unc Tg(HLA-A24/H2-D/B2M)3Dvs/J 005512 NOD.B6-Tg(HLA-A2.1)1Enge/DvsJ 004548 NOD.Cg-B2mtm1Unc Tg(B2M)55Hpl Tg(HLA-A2.1)1Enge/DvsJ 004262 NOD.Cg-Prkdcscid Tg(HLA-A2.1)1Enge/Dvs 009617 NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(HLA-A2.1)1Enge/SzJ 006609 NOD.Cg-Prkdcscid Tg(HLA-A2.1)1Enge/DvsJ 005853 NOD.Cg-Tg(HLA-A2/H2-K)1Scr/ShrmJView Strains carrying other alleles of HLA-A (9 strains)Strains carrying other alleles of HLA-A2.1
004191 B6.Cg-Tg(HLA-A/H2-D)2Enge/J 003475 C57BL/6-Tg(HLA-A2.1)1Enge/J 005512 NOD.B6-Tg(HLA-A2.1)1Enge/DvsJ 004548 NOD.Cg-B2mtm1Unc Tg(B2M)55Hpl Tg(HLA-A2.1)1Enge/DvsJ 004262 NOD.Cg-Prkdcscid Tg(HLA-A2.1)1Enge/Dvs 009617 NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(HLA-A2.1)1Enge/SzJ 006609 NOD.Cg-Prkdcscid Tg(HLA-A2.1)1Enge/DvsJ 005853 NOD.Cg-Tg(HLA-A2/H2-K)1Scr/ShrmJView Strains carrying other alleles of HLA-A2.1 (8 strains)
View Related Disease (OMIM) TermsRelated Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
- 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.View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
- 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 ApplicationsResearch ApplicationsThis 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
Type 1 Diabetes
CD Antigens, Antigen Receptors, and Histocompatibility Markers
|Allele Name||transgene insertion 1, David Serreze|
|Allele Type||Transgenic (Inserted expressed sequence)|
|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]|
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]
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]
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]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
|Pricing for USA, Canada and Mexico shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2140.00
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.
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|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2782.00
Cryorecovery - Standard.
Progeny testing is not required.
|Considerations for Choosing Controls|
|Control Pricing Information for Genetically Engineered Mutant Strains.|
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