JAX
Mouse Strain Datasheet - 004606
NOD.Cg-Prkdcscid H2-Ab1tm1Doi Tg(HLA-DQA1,HLA-DQB1)1Dv/SzJ
- Stock No:
- 004606 |
- NOD.scid AB0nullDQ8
Also Known As: NOD.scid AB0nullDQ8
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.
Donating Investigator
Dr. Leonard D. Shultz, The Jackson Laboratory
Genetic overview
| Genetic Background | Generation |
|---|---|
|
001289 NOD/ShiLt |
|
H2-Ab1tm1Doi
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout) | H2-Ab1 | histocompatibility 2, class II antigen A, beta 1 |
Prkdcscid
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Spontaneous | Prkdc | protein kinase, DNA activated, catalytic polypeptide |
Tg(HLA-DQA1,HLA-DQB1)1Dv
| Allele Type |
|---|
| Transgenic (Humanized sequence, Inserted expressed sequence) |
Research Applications
- Diabetes and Obesity Research
- Immunology, Inflammation and Autoimmunity Research
- Research Tools
- Internal/Organ Research
- Virology Research
Detailed Description
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.
Development
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 Schultz et al (Unpublished), backcrossed the NOD-Tg(HLA-DQ8)1Sz H2-Ab1tm1Doi to NOD.Cg-Prkdcscid H2-Ab1tm1Doi/Sz.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.
Expression Data
| 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 |
| Site of Expression |
Control Suggestions
- Prkdcscid/Prkdcscid, H2-Ab1/H2-Ab1, +/+
- Noncarrier
Additional Information
H2-Ab1tm1Doi
Allele Symbol: H2-Ab1tm1Doi
| Allele Name | targeted mutation 1, Christophe Benoist and Diane Mathis |
|---|---|
| Allele Type | Targeted (Null/Knockout) |
| Allele Synonym(s) | A beta0; Abbeta-; AB0; Abeta-; Class II0; H2-Ab1tm1Dim; H2-Ab1tm1Doi; II0; MHC class II-; MHC-II-k.o.; MHCII- |
| Gene Symbol and Name | H2-Ab1, histocompatibility 2, class II antigen A, beta 1 |
| Gene Synonym(s) | A beta; AI845868; Abeta; Bb; CELIAC1; H-2Ab; H-2Ab; H2-Ab; H2-Ab; HLA-DQB; I-Ab; I-Abeta; I-region-associated antigen 2; IAb; IDDM1; Ia-2; Ia-2; Ia2; Ia2; RT1.B; Rmcs1; Rmcs1; expressed sequence AI845868; histocompatibility 2, class II antigen A, beta; response to metastatic cancers 1 |
| 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 |
Prkdcscid
Allele Symbol: Prkdcscid
| Allele Name | severe combined immunodeficiency |
|---|---|
| Allele Type | Spontaneous |
| Allele Synonym(s) | SCID; scid |
| Gene Symbol and Name | Prkdc, protein kinase, DNA activated, catalytic polypeptide |
| Gene Synonym(s) | AI326420; AU019811; DNA-PK; DNA-PKcs; DNAPDcs; DNAPK; DNPK1; DOXNPH; HYRC; HYRC1; IMD26; XRCC7; doxorubicin nephropathy; dxnph; dxnph; expressed sequence AI326420; expressed sequence AU019811; p350; scid; severe combined immunodeficiency; slip |
| Site of Expression | T and B lymphocytes. |
| Strain of Origin | C.B-17 |
| Chromosome | 16 |
| Molecular Note | A T-to-A transversion point mutation at a position corresponding to codon 4095 created a premature stop codon. |
Tg(HLA-DQA1,HLA-DQB1)1Dv
Allele Symbol: Tg(HLA-DQA1,HLA-DQB1)1Dv
| Allele Name | transgene insertion 1, Chella David |
|---|---|
| Allele Type | Transgenic (Humanized sequence, Inserted expressed 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) | Abeta0.DQ8; DQ8; HLA-DQ8; HLA-DQ8 Tg; Tg(HLA-DQA1*301,HLA-DQB1*302)1Dv |
| 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-H2 |
| 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 |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Diabetes and Obesity Research
- Type 1 Diabetes (IDDM)
- Type 1 Diabetes (IDDM) Analysis Strains
- NOD Congenics with Mutations Affecting Immunocompetence
- Immunology, Inflammation and Autoimmunity Research
- HLA transgenics
- Immunodeficiency
- MHC class II deficient
- Research Tools
- Immunology, Inflammation and Autoimmunity Research
- MHC class II defects
- Immunology, Inflammation and Autoimmunity Research
Genotype: Prkdcscid related
- Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
- B and T cell deficiency
- Immunodeficiency
- Internal/Organ Research
- Lymphoid Tissue Defects
- B and T cell deficiency
- Lymphoid Tissue Defects
- Research Tools
- Cancer Research
- B and T cell deficiency, xenograft/transplant host
- Toxicology Research
- xenograft/transplant host
- Cancer Research
- Virology Research
- B and T Cell Deficiency
- AIDS research tool
- B and T Cell Deficiency
References
Additional - H2-Ab1tm1Doi related
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