Strain Name: |
NOD.Cg-Prkdcscid H2-Ab1tm1Doi Tg(HLA-DQA1,HLA-DQB1)1Dv/SzJ |
|---|---|
Stock Number: |
004606 |
Availability: | Repository-Cryopreserved |
General Terms and Conditions |
| Former Name |
NOD.Cg-Prkdcscid H2-Ab1tm1Doi Tg(HLA-DQA1*301,HLA-DQB1*302)1Dv/SzJ (Changed: 17-AUG-06
) |
|
NOD.Cg-Prkdcscid H2-Ab1tm1Dim Tg(HLA-DQA1*301,HLA-DQB1*302)1Dv/SzJ (Changed: 15-DEC-05
) | |
|
NOD.Cg-Prkdcscid Tg(HLA-DQ8)1Sz H2-Ab1tm1Dim/SzJ (Changed: 02-SEP-05
) | |
| Genes & Alleles | H2-Ab1; H2-Ab1tm1Doi; HLA-DQA1; HLA-DQB1; Prkdc; Prkdcscid; Tg(HLA-DQA1,HLA-DQB1)1Dv; |
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 - Spontaneous Mutation Type JAX® GEMM® Strain - Targeted Mutation Type JAX® GEMM® Strain - Transgenic Species laboratory mouse Background Strain NOD/ShiLt Donor Strain Multiple: B10.M, 129, B6 Donating Investigator Leonard Shultz, The Jackson Laboratory Generation NE10F?+1p (12-JUN-05) Appearance
albino, pink eyed
Related Genotype: A/A Tyrc/TyrcStrain 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.Strain 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 targeteed 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 Schultz et al (Unpublished), backcrossed the NOD-Tg(HLA-DQ8)1Sz H2-Ab1tm1Doi to NOD.Cg-Prkdcscid H2-Ab1tm1Doi/Sz.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.
Gene & Allele Details
| Allele Symbol | H2-Ab1tm1Doi | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Christophe Benoist and Diane Mathis | ||
| Common Name(s) | A beta<0>; Abeta-; Class II<0>; H2-Ab1tm1Dim; II0; MHC class II-; MHC-II-k.o.; | ||
| Mutation Made By | Christophe Benoist, Joslin Diabetes Center | ||
| Strain of Origin | 129S2/SvPas | ||
| ES Cell Line Name | D3 | ||
| ES Cell Line Strain | 129S2/SvPas | ||
| Gene Symbol and Name | H2-Ab1, histocompatibility 2, class II antigen A, beta 1 | ||
| Chromosome | 17 | ||
| Gene Common Name(s) | A beta; AI845868; Abeta; CELIAC1; H-2Ab; H2-Ab; HLA-DQB; I-Ab; I-Abeta; I-region-associated antigen 2; IAb; IDDM1; Ia-2; Ia2; Rmcs1; expressed sequence AI845868; histocompatibility 2, class II antigen A, beta; response to metastatic cancers 1; | ||
| 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. [MGI Ref ID J:65736] | ||
| Allele Symbol | Prkdcscid | ||
| Allele Name | severe combined immunodeficiency | ||
| Common Name(s) | scid; | ||
| Strain of Origin | CB17 | ||
| Gene Symbol and Name | Prkdc, protein kinase, DNA activated, catalytic polypeptide | ||
| Chromosome | 16 | ||
| Gene Common Name(s) | AI326420; AU019811; DNA-PK; DNA-PKcs; DNAPDcs; DNAPK; DNPK1; HYRC; HYRC1; XRCC7; expressed sequence AI326420; expressed sequence AU019811; p350; scid; severe combined immunodeficiency; slip; | ||
| General Note |
The Prkdcscid mutation arose in the C.B-17 inbred strain (BALB/c.C57BL/Ka-Igh-1b) (J:9341). Most homozygotes have no detectable IgM, IgG1, IgG2a, IgG2b, IgG3, or IgA, but a few have low levels of one to three of these immunoglobulin isotypes. The size of the lymphoid organs is only one-tenth or less that of normal. Thymus, lymph nodes, and splenic follicles are virtually devoid of lymphocytes (J:30980). Homozygotes are deficient in both B and T cell function. Their spleen cells do not respond to either B or T cell mitogens and they are unable to reject skin grafts. They lack detectable B cells and pre-B cells. In spite of the small thymus and lack of functional T cells, the Thy1 marker is present on a majority of cells recovered from the thymus, and T cell lymphomas occur in 10 per cent or more of affected mice. Prkdcscid specifically impairs differentiation of stem cells into mature lymphocytes. Myeloid cell differentiation is not affected. The basic defect in these mice appears to be in the lymphoid stem cells and not in the cellular environment, since functional T and B cells are found in mice reconstituted with normal bone marrow (J:30980, J:7343). However, full reconstitution of the immune deficiency occurs only after irradiation of the recipients, indicating that Prkdcscid/Prkdcscid mice may have normal numbers of a radiation-sensitive stem cell that has defective proliferative capacity (J:8299). The rearrangements of immunoglobulin and T cell receptor genes that normally occur in B and T lymphocytes are not found in homozygous Prkdcscid mice. However, in Abelson leukemia virus-transformed B cells of these mice and in their occasional T cell lymphomas, rearrangements, most of which are abnormal, are found. This suggests that scid may act through an effect on the recombinase system catalyzing the assembly of immunoglobulin and T cell receptor genes, and that lymphocytes with these defects are not able to develop further (J:8420). Although most Prkdcscid homozygotes fail to produce immunoglobulin and functional T-cell receptor, some produce these products at low levels, with an occasional mouse with nearly normal levels of serum immunoglobulin, the criterion usually used tomeasure the effects of Prkdcscid. This phenomenon is referred to as "leakiness" of the VDJ recombination defect (J:4610).Homozygous Prkdcscidmice are fertile and, under specific pathogen-free conditions, may survive a year or more(J:6958). The Prkdcscid mouse has been widely used in studies of the immune system, in particular of VDJ recombination in T and B lymphocytes. Its lack of immunocompetence has made it useful in transplantation studies, particularly transplantation and development of metastasis in human tumors. The interaction of infection, immunity, and disease processes have been studied with these mice. Poole (J:31292) offers a brief review of the nature and usefulness of the Prkdcscid mouse, with key references to the very extensive literature. Mutant mRNA does not appear to differ from wild type although protein expression is reduced more than 10-fold. Mutant protein is defective for nuclear association but exhibits normal DNA-binding ability. NOD.Cg-Prkdcscid B2mtm1Unc mice lack mature lymphocytes and serum Ig, are MHC class I deficient, B and T cell deficient, C-5 deficient (Hc0), and have low NK cells. These mice display accumulation of iron in the liver and rapid clearance of human IgG1. | ||
| Molecular Note | A T-to-A transversion point mutation at a position corresponding to codon 4095 created a premature stop codon. [MGI Ref ID J:35393] [MGI Ref ID J:39329] | ||
| Allele Symbol | Tg(HLA-DQA1,HLA-DQB1)1Dv | ||
| Allele Name | transgene insertion 1, Chella David | ||
| Common Name(s) | Abeta0.DQ8; DQ8; HLA-DQ8; HLA-DQ8 Tg; Tg(HLA-DQA1*301,HLA-DQB1*302)1Dv; | ||
| Mutation Made By | Chella David, | ||
| Strain of Origin | (CBA/J x B10.M-H2 | ||
| 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 | ||
| Promoter | HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, human | ||
| Promoter | HLA-DQB1, major histocompatibility complex, class II, DQ beta 1, human | ||
| 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. [MGI Ref ID J:88296] | ||
Control Information
| Control | ||
|---|---|---|
| Prkdcscid/Prkdcscid, H2-Ab1/H2-Ab1, +/+ | ||
| Noncarrier | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Prkdcscid
Colony Maintenance
| Breeding & Husbandry | 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. |
|---|---|
| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
Strains carrying H2-Ab1tm1Doi allele
005589 NOD.Cg-Prkdcscid H2-Ab1tm1Doi/SzJ View Strains carrying H2-Ab1tm1Doi (1 strain)
Additional Web Information
Congenic Nomenclature
Genetic Quality Control Annual Report
Research Applications
This mouse can be used to support research in many areas including:
Prkdcscid relatedDiabetes and Obesity Research
Type 1 Diabetes (IDDM)
Type 1 Diabetes (IDDM) Analysis Strains (NOD Congenics with Mutations Affecting Immunocompetence)
Immunology and Inflammation Research
Immunodeficiency (MHC class II deficient)
Rearranged Antigen-Specific T Cell Receptor Transgenes (class II restricted)
Research Tools
Immunology and Inflammation Research (MHC class II defects)
Immunology and Inflammation Research
Immunodeficiency (B and T cell deficiency)
Internal/Organ Research
Lymphoid Tissue Defects (B and T cell deficiency)
Research Tools
Cancer Research (B and T cell deficiency) (xenograft/transplant host)
Toxicology Research (xenograft/transplant host)
Virology Research
B and T Cell Deficiency (AIDS research tool)
References
Additional ReferencesPrice and Supply Information
| Strain Name: | NOD.Cg-Prkdcscid H2-Ab1tm1Doi Tg(HLA-DQA1,HLA-DQB1)1Dv/SzJ |
| Stock Number: | 004606 |
Price Details
IMPORTANT NOTE: Prices are based on shipping destination. To view prices, select your shipping destination.
*NO Shipping Destination selected!
Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. |
| Licensing | See General Terms and Conditions below |
| Control Information | View Control Information in Strain Details. |
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
The Jackson Laboratory's Genotype Promise
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.Ordering and Purchasing Information
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form