This strain which is MHC II deficient and has no functional T or B cells expresses a humanized transgenic HLA-DQ8 molecule that has been linked to IDDM development. This model is a valuable genetic tool for identifying the role of HLA-DQ8 in Type 1 Diabetes.
Dr. Leonard D. Shultz, The Jackson Laboratory
Genetic Background | Generation |
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001289 NOD/ShiLt |
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Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Prkdc | protein kinase, DNA activated, catalytic polypeptide |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | H2-Ab1 | histocompatibility 2, class II antigen A, beta 1 |
Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
This strain which is MHC II deficient and has no functional T or B cells expresses a humanized transgenic HLA-DQ8 molecule that has been linked to IDDM development. This model is a valuable genetic tool for identifying the role of HLA-DQ8 in Type 1 Diabetes.
A 30kb DNA fragment containing the DQA*0301 gene from cosmid H11A and a 38kb DNA fragment containing the DQB*0302 gene from cosmid X10A were microinjected into (CBA/J x B10.M)F2 embryos. To establish germline transmission founders were mated to the B10.M strain. This transgene was then mated to (B6x129)-H2-Ab1 targeted mutation. The transgene positive, H2-Ab1 mice were intercrossed to make homozygote for the H2-Ab1 targeted allele (Nabozny et al, 1996). Flynn et al, 2002, backcrossed the transgenic HLA-DQ8, H2-Ab1 mice to NOD for 10 generations. Schultz et al (Unpublished), backcrossed the NOD-Tg(HLA-DQ8)1Sz H2-Ab1tm1Doi to NOD.Cg-Prkdcscid H2-Ab1tm1Doi/Sz. In 2003, the Type 1 Diabetes Resource received NOD.Cg-PrkdcscidTg(HLA-DQ8)1Sz H2-Ab1tm1Doi/Sz at [NE10F?+4p]+F1.
Expressed Gene | HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, human |
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Expressed Gene | HLA-DQB1, major histocompatibility complex, class II, DQ beta 1, human |
Site of Expression |
Allele Name | severe combined immunodeficiency |
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Allele Type | Spontaneous |
Allele Synonym(s) | SCID |
Gene Symbol and Name | Prkdc, protein kinase, DNA activated, catalytic polypeptide |
Gene Synonym(s) | |
Site of Expression | T and B lymphocytes. |
Strain of Origin | C.BKa-Ighb/Icr |
Chromosome | 16 |
Molecular Note | A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*). |
Allele Name | targeted mutation 1, Christophe Benoist and Diane Mathis |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | A beta0; Abbeta-; AB0; Abeta-; Class II0; H2-Ab1tm1Dim; H2-Ab1tm1Doi; II0; MHC class II-; MHCII-; MHC-II-k.o. |
Gene Symbol and Name | H2-Ab1, histocompatibility 2, class II antigen A, beta 1 |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 17 |
Molecular Note | The second exon was disrupted by the insertion of a neomycin resistance gene. In addition, the ES cell line used was derived from the 129S2/SvPas strain, which carries a deletion in the promoter region of H2-Ea. Consequently, these MHC class II molecule-deficient mice lacked cell surface expression of both class II-A and class II-E MHC proteins. |
Mutations Made By | Christophe Benoist, Joslin Diabetes Center |
Allele Name | transgene insertion 1, Chella David |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | Abeta0.DQ8; DQ8; HLA-DQ8; HLA-DQ8 Tg; HLA-DQA1*0301/DQB1*0302; Tg(HLA-DQA1*301,HLA-DQB1*302)1Dv |
Gene Symbol and Name | Tg(HLA-DQA1,HLA-DQB1)1Dv, transgene insertion 1, Chella David |
Gene Synonym(s) | |
Promoter | HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, human |
Promoter | HLA-DQB1, major histocompatibility complex, class II, DQ beta 1, human |
Expressed Gene | HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, human |
Expressed Gene | HLA-DQB1, major histocompatibility complex, class II, DQ beta 1, human |
Strain of Origin | (CBA/J x B10.M-H2f)F2 |
Chromosome | UN |
General Note | Flow cytometric analysis of peripheral blood leukocytes (PBL) using a monoclonal antibody to HLA-DQ demonstrated that transgenic mice express the transgenes. 25-40% of the PBLs of mixed-background transgenic mice homozygous for the targeted MHC class II mutation H2-Ab1tm1Dim express the transgenes. Lymph nodes of such mice contain three-fold the levels of CD4+ CD44+ T-cells as do those of nontransgenic MHC class II-deficient mice, levels similar to those of class II-sufficient mice. Immunization of transgenic H2-Ab1tm1Dim homozygous mice with bovine collagen II results in a strong IgG antibody response to the immunogen, and 66% of these mice develop severe, persistent arthritis. (J:88296) |
Molecular Note | A 30-kb human genomic DNA fragment containing the entire HLA-DQA1*0301 gene and a promoter-truncated HLA-DQB1*0302 gene from cosmid H11A and a 38-kb DNA fragment containing the entire HLA-DQB1*0302 gene from cosmid X10A were coinjected. |
Mutations Made By | Chella David, Mayo Clinic |
These mice are immunodeficient and need to be maintained in a high barrier environment with sterile food and water or given antibiotic in the water.
Embryos frozen are either Prkdcscid/Prkdcscid, Tg/+, H2-Ab1tm1Doi/H2-Ab1tm1Doi or Prkdcscid/Prkdcscid, +/+, H2-Ab1tm1Doi/H2-Ab1tm1Doi
Recommended breeding scheme: Prkdcscid/Prkdcscid, Tg/+, H2-Ab1tm1Doi/H2-Ab1tm1Doi X Prkdcscid/Prkdcscid, +/+, H2-Ab1tm1Doi/H2-Ab1tm1Doi and reciprocal.
Affected mutant: Prkdcscid/Prkdcscid, Tg/+, H2-Ab1tm1Doi/H2-Ab1tm1Doi.
When using the NOD.scid AB0nullDQ8 mouse strain in a publication, please cite the originating article(s) and include JAX stock #004606 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous for Prkdc<scid>, Homozygous for H2-Ab1<tm1Doi> , Hemizygous or Homozygous(Tg/?) or no-carrier for Tg(HLA-DQA1,HLA-DQB1)1Dv |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> H2-Ab1<tm1Doi> Tg(HLA-DQA1 HLA-DQB1)1Dv/S | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> H2-Ab1<tm1Doi> Tg(HLA-DQA1 HLA-DQB1)1Dv/S | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> H2-Ab1<tm1Doi> Tg(HLA-DQA1 HLA-DQB1)1Dv/S | $3373.50 |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> H2-Ab1<tm1Doi> Tg(HLA-DQA1 HLA-DQB1)1Dv/S | $3373.50 |
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