Strain Name: |
NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ |
|---|---|
Stock Number: |
005557 |
Availability: | Level 3 |
General Terms and Conditions |
| Strain Common Names | NOD-scid IL2Rgammanull; NOD-scid IL2Rgnull; |
| Genes & Alleles | Il2rg; Il2rgtm1Wjl; Prkdc; Prkdcscid; |
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 Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Donating Investigator Leonard Shultz, The Jackson Laboratory H2 Haplotype g7 Generation N8F?+4pF2 (03-JAN-08) Appearance
albinoStrain Description
These mutant mice do not express the Prkdc gene nor the X-linked Il2rg gene. Mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Histological examination of lymphoid tissues reveals absence of lymphoid cells and some cystic structures in the thymus, an absence of follicles in the spleen and markedly diminished celluarity of lymph nodes. Double mutants are deficient in mature lymphocytes, serum Ig is not detectable and natural killer (NK) cell cytotoxic activity is extremely low. These mice are resistant to lymphoma development even after sublethal irradiation treatment. These mice have been shown to readily support engraftment of human CD34+ hematopoietic stem cells and represent a superior, long-lived model suitable for studies employing xenotransplantation strategies.Strain Development
These double mutant mice were produced by breeding female NOD.CB17-Prkdcscid/J (Stock No. 001303) mice with male mice bearing the X-linked B6.129S4-Il2rgtm1Wjl/J allele (Stock No. 003174). The resulting male mice heterozygous for the Prkdcscid allele and hemizygous for the Il2rgtm1Wjl allele were crossed to female NOD.CB17-Prkdcscid/J (Stock No. 001303) mice for 8 generations. Heterozygotes were interbred to produce mice homozygous for the Prkdcscid allele and homozygous (females) or hemizygous (males) for the Il2rgtm1Wjl allele.
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Il2rgtm1Wjl | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Warren J Leonard | ||
| Common Name(s) | CD132-; IL2Rgammanull; [KO]gammac; gammac-; | ||
| Mutation Made By | Warren Leonard, NHLBI, NIH | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/SvJae | ||
| Gene Symbol and Name | Il2rg, interleukin 2 receptor, gamma chain | ||
| Chromosome | X | ||
| Gene Common Name(s) | Ab2-183; CD132; IMD4; SCIDX; SCIDX1; [g]c; common cytokine receptor gamma chain; common gamma chain; gamma C receptor; gamma(c); | ||
| Molecular Note | A neomycin resistance cassette replaced part of exon 3 and all of exons 4 - 8 of the gene, resulting in the loss of most of the extracellular domain and all of the transmembrane and cytoplasmic domains of the protein. [J:24117] | ||
| 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. [J:35393] [J:39329] | ||
Control Information
| Control | ||
|---|---|---|
| 001303 NOD.CB17-Prkdcscid/J | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Il2rgtm1Wjl
Prkdcscid
Colony Maintenance
| Breeding & Husbandry | When maintaining a live colony, these mice are bred as homozygotes for both the Prkdcscid and Il2rgtm1Wjl alleles. SPF (specific pathogen-free) conditions are recommended. |
|---|---|
| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
Strains carrying Il2rgtm1Wjl allele
003174 B6.129S4-Il2rgtm1Wjl/J 003169 C.129S4-Il2rgtm1Wjl/J View Strains carrying Il2rgtm1Wjl (2 strains)
002479 STOCK Il2rgtm1Cgn/J
Additional Web Information
Genetic Quality Control Annual Report
JAX Notes, Spring 2006; 501. Choosing an Immunodeficient Mouse Model.
JAX Notes, Spring 2008; 509. Jackson Laboratory's Leonard Shultz PhD Helps Develop a Better Leukemia Mouse Model.
JAX Notes, Summer 2005; 498. NOD.Cg-Prkdcscid Il2rgtm1Wjl/Sz, a New Model for Engraftment with Human Hematopoietic Stem Cells.
Strain-at-a-glance.
Animal Health Reports
Room Number AX30
Room Number WR3
Research Applications
This mouse can be used to support research in many areas including:
Il2rgtm1Wjl relatedResearch Tools
Immunology and Inflammation Research (B, T, and NK cell deficiency)
Prkdcscid relatedCancer Research
Growth Factors/Receptors/Cytokines
Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
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
Selected Reference(s)
Additional ReferencesShultz LD; Lyons BL; Burzenski LM; Gott B; Chen X; Chaleff S; Kotb M; Gillies SD; King M; Mangada J; Greiner DL; Handgretinger R. 2005. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol 174(10):6477-89. [PubMed: 15879151] [J:109833]
Price and Supply Information
| Strain Name: | NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ |
| Stock Number: | 005557 |
Price Details
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Supply Details
| Standard Supply | Level 3. Up to 50 mice. Larger quantities or custom orders arranged upon request. |
|---|---|
| Supply Notes |
Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available. Strains that must be genotyped are not available until five to seven weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View 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.Ordering and Purchasing Information
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