Strain Name: |
NOD.Cg-Prkdcscid Tg(Ins2-GAD2)1Lt/LtJ |
|---|---|
Stock Number: |
003843 |
Availability: | Repository-Cryopreserved |
General Terms and Conditions |
| Former Name |
NOD/LtSz-Prkdcscid Tg(Ins2-GAD2)1Lt/LtJ (Changed: 01-DEC-05
) |
|
NOD.Cg-Prkdcscid Tg(GAD2)1Lt (Changed: 28-NOV-05
) | |
|
NOD/Lt-Prkdcscid Tg(GAD2)1Lt (Changed: 15-DEC-04
) | |
| Genes & Alleles | GAD2; Ins2; Prkdc; Prkdcscid; Tg(Ins2-GAD2)1Lt; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Coisogenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Congenic Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Spontaneous Mutation Type JAX® GEMM® Strain - Transgenic Species laboratory mouse Donating Investigator Edward Leiter, The Jackson Laboratory H2 Haplotype g7 Appearance
albino, pink eyed
Related Genotype: A/A Tyrc/TyrcStrain Description
NOD.Cg-Prkdcscid Tg(Ins2-GAD2)1Lt/LtJ transgenic mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Transgenic mice are homozygous for Prkdcscid and are free of potential insulitic lymphocytes resulting in diabetes resistance. Similar to the NOD/Lt-Tg(Ins2-GAD2)1Lt (Stock No. 003074) the transgene inserted into Chromosome Y, thus only males are transgenic (Bridgett et al, Diabetes 1998 47:1848-56).This model provides a tool for studying the role of GAD2 as a islet autoantigen in the NOD mouse model of Type 1 diabetes.
Strain Development
The transgene Ins2-GAD2 encodes the human glutamic acid decarboxylase2 cDNA under the control of the rat insulin 2 promoter. This transgenic construct was injected into NOD/Lt oocytes and the resulting founders were backcrossed to wildtype siblings. NOD transgenic mice were backcrossed 1 generation to NOD.CB17-Prkdcscid prior to intercrossing to make homozygote for the Prkdcscid mutation (Bridgett et al, Diabetes 1998 47:1848-56). In 2005, the Type 1 Diabetes Resource received NOD/LtSz-Prkdcscid Tg(Ins2-GAD2)1Lt/LtJ at generation N2F21.
Gene & Allele Details
| 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(Ins2-GAD2)1Lt | ||
| Allele Name | transgene insertion 1, Edward H Leiter | ||
| Common Name(s) | TgN(RIP7hGAD65)Lt4 Y-line; | ||
| Strain of Origin | NOD/ShiLt | ||
| Expressed Gene | GAD2, glutamate decarboxylase 2 (pancreatic islets and brain, 65kDa), human | ||
| Promoter | Ins2, insulin 2, rat | ||
| Molecular Note | The transgene comprises the cDNA sequence encoding human glutamic acid decarboxylase 2 under control of a modified rat insulin 2 promoter composed of 9.5 kb of genomic DNA from upstream of the transcription initiation site fused to the first intron of Ins2. Transmission from the founder male only to male progeny demonstrated integration into the Y chromosome. Densitrometric Southern blot analysis indicates presence of approximately 17 copies of the transgene. Expression in the pancreatic islets of transgenic mRNA has been demonstrated by reverse transcription followed by PCR (RT-PCR), and of GAD2 protein by western blot analysis. [MGI Ref ID J:100251] | ||
Control Information
| Control | ||
|---|---|---|
| Wild-type female from the colony | ||
| 001303 NOD.CB17-Prkdcscid/J | ||
| 003074 NOD/ShiLt-Tg(Ins2-GAD2)1Lt/LtJ | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Prkdcscid
Tg(Ins2-GAD2)
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. |
|---|---|
| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
Strains carrying Prkdcscid allele
View Strains carrying Prkdcscid (25 strains)
003074 NOD/ShiLt-Tg(Ins2-GAD2)1Lt/LtJ
003844 NOD.Cg-Prkdcscid Tg(Ins2-GAD2)2Lt/LtJ 005870 NOD/ShiLt(Cg)-Tg(Ins2-GAD2)2Lt/J
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 relatedResearch Tools
Immunology and Inflammation Research (B and T cell deficiency)
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 Tg(Ins2-GAD2)1Lt/LtJ |
| Stock Number: | 003843 |
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