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Strain Name:

NOD.129P2(B6)-B2mtm1Unc Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ

Stock Number:

006611

Availability:

Repository- Live

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General Terms and Conditions

Strain Common Names      NOD.B.2mnull.HHD;      NOD.beta2m-.HHD;
Genes & Alleles   B2M;   B2m;   B2mtm1Unc;   H2-D;   HLA-A;   HLA-A2.1;   Tg(HLA-A/H2-D/B2M)1Dvs;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Targeted Mutation
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Background Strain NOD
Donor Strain 129P2 derived E14TG2a ES cell line
Donating Investigator David Serreze,   The Jackson Laboratory
H2 Haplotypeg7
GenerationN1F1 (13-MAY-08)

Appearance
albino, pink eyed

Related Genotype: A/A Tyrc/Tyrc

Strain Description
NOD mice carrying only the HLA-A/H2-D/B2M transgene, commonly referred to as NOD.HHD, (Stock No. 006604) develop significantly accelerated diabetes onset compared to NOD/ShiLtDvs (NOD) inbred mice. This mutant stock is also homozygous for the B2mtm1Unc mutation which normally prevents the development of of CD8+ T cells. The presence of the transgene in the B2m-deficient background, however, restores CD8+ T cells, but at a significantly lower level than in NOD inbred mice. Due to the covalently linked nature of the B2M component encoded into the transgene, the transgenic construct is unable to rescue murine MHC class 1 molecules in the NOD.B2m deficient (Stock No. 002309) mice. Thus, these double mutant mice only express human HLA-A2.1. Fifty-five percent of these NOD transgenic B2m-deficient mice develop diabetes by 30 weeks of age, while non-transgenic NOD.B2mtm1Unc do not develop diabetes. Insulitis scores assessed via histological examination of pancreata are similar between NOD/ShiLtDvs and NOD transgenic B2m-deficient mice. Although CD8+ T cell numbers in NOD transgenic B2m-deficient are lower than in NOD inbred mice, comparable numbers of CD8+ T cells can be cultured from pancreatic islets from both strains. The infiltrating T cells cultured from the double mutant islets are HLA-A2.1-specific, and are able to recognize islet specific antigens, such as IGRP.

NOD transgenic mice carrying the Prkdcscid (Stock No. 006605) do not become diabetic.

This model provides humanized T cells that will be useful tools to identify MHC class I epitopes recognized by CD8+ T cells in type 1 diabetes patients and for testing new therapies focused on restoring immune tolerance.

Strain 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 No. 006604 - NOD/ShiLtDvs-Tg(HLA-A/H2-D/B2M)1Dvs/J at generation N1F15. Stock No. 006604 was crossed to Stock No. 002309 - NOD.129P2(B6)-B2mtm1Unc/J. The resulting offspring were sibling mated to provide double mutant HLA transgenic, B2m deficient mice.

Related Disease (OMIM) Terms

Diabetes Mellitus, Insulin-Dependent; IDDM
Mammalian Phenotype Terms assigned by genotype

B2mtm1Unc/B2mtm1Unc Tg(HLA-A/H2-D/B2M)1Dvs/0

        NOD.Cg-B2mtm1Unc Tg(HLA-A/H2-D/B2M)1Dvs
  • immune system phenotype
  • abnormal cell-mediated immunity (MGI Ref ID J:121685)
    • HLA-A2.1-restricted T cells from mice as young as 5 weeks of age respond to IGRP (islet-specific glucose-6-phophatase catalytic subunit-related protein) peptides
    • abnormal CD8-positive T cell physiology (MGI Ref ID J:121685)
      • islet-infiltrating T cells show different patterns of recognition to various IGRP peptides; peptide 228-236 is immunodominant HLA-A2.1-binding epitope of IGRP in 12-13 week old nondiabetic female mice
      • abnormal cytotoxic T cell physiology (MGI Ref ID J:121685)
        • T cells from islets show HLA-A2-restricted cytotoxicity against human HLA-A2.1-positive human pancreatic islets, as well as mouse islets
  • decreased CD8-positive T cell number (MGI Ref ID J:121685)
    • CD8+ T cells develop, but at significantly reduced numbers (~10%) compared to NOD controls
  • increased susceptibility to autoimmune diabetes (MGI Ref ID J:121685)
    • 55% of females develop type I diabetes by 30 weeks of age, with significantly accelerated onset compared with non transgenic littermates
  • hematopoietic system phenotype
  • decreased CD8-positive T cell number (MGI Ref ID J:121685)
    • CD8+ T cells develop, but at significantly reduced numbers (~10%) compared to NOD controls

Gene & Allele Details

Allele Symbol B2mtm1Unc
Allele Name targeted mutation 1, University of North Carolina
Common Name(s) I0; b2mnull; beta2-m-KO; beta2M-; beta2MKO; beta2m0; beta2mnull; beta2mo; beta2mtm1Unc;
Mutation Made By Oliver Smithies,   University of North Carolina
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14TG2a
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name B2m, beta-2 microglobulin
Chromosome 2
Gene Common Name(s) Ly-m11; beta 2 microglobulin; beta2-m; lymphocyte antigen m11;
Molecular Note Insertion of a neomycin-resistance gene into the second exon. [MGI Ref ID J:65612]
 
Allele Symbol Tg(HLA-A/H2-D/B2M)1Dvs
Allele Name transgene insertion 1, David Serreze
Common Name(s) HDD; HHD;
Mutation Made By 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
Expressed Gene H2-D, histocompatibility 2, D region, mouse, laboratory
Promoter HLA-A2.1, HLA-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]

Control Information

  Control
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls

Genotyping Protocols

B2mtm1Unc
Tg(HLA-A/H2-D)
Tg(HLA-A/H2-D) QPCR

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying   B2mtm1Unc     (19 strains)

Strains carrying   Tg(HLA-A/H2-D/B2M)1Dvs allele
006605   NOD.Cg-Prkdcscid Emv30b Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ
006604   NOD/ShiLtDvs-Tg(HLA-A/H2-D/B2M)1Dvs/J
View Strains carrying   Tg(HLA-A/H2-D/B2M)1Dvs     (2 strains)

View Strains carrying other alleles of B2M     (5 strains)

Strains carrying other alleles of H2-D
006125   FVB-Tg(H2-D-Il15)3304Clgr/J
View Strains carrying other alleles of H2-D     (1 strain)

View Strains carrying other alleles of HLA-A     (7 strains)

Additional Web Information

Congenic Nomenclature

Animal Health Reports

Room Number           AX11

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 and Inflammation Research
Autoimmunity (Type 1 Diabetes)

Research Tools
Immunology and Inflammation Research (T cell deficiency)

HLA-A related

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Vaccine Development

B2mtm1Unc related

Hematological Research
Anemia, Iron Deficiency and Transport Defects (hemochromatosis)

Immunology and Inflammation Research
Immunodeficiency (MHC class I deficiency)

Internal/Organ Research
Liver Defects (hemochromatosis)

Metabolism Research
Hemochromatosis (iron metabolism defects)

Research Tools
Immunology and Inflammation Research (MHC class I deficiency)

References

Selected Reference(s)

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]

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

Price and Supply Information

Strain Name: NOD.129P2(B6)-B2mtm1Unc Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ
Stock Number: 006611

Price Details

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Type 1 Diabetes Repository collection.
LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

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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.
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