Strain Name: |
NOD.Cg-Cd38tm1Lnd Prkdcscid/LtJ |
|---|---|
Stock Number: |
005345 |
Availability: | Repository-Cryopreserved |
General Terms and Conditions |
| Strain Common Names | NOD.Cg-Cd38tm1Lnd Prkdcscid/Lt; |
| Genes & Alleles | Cd38; Cd38tm1Lnd; 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 Species laboratory mouse Background Strain NOD/ShiLt Donor Strain B6.129P2/OlaHsd Donating Investigator Edward Leiter, The Jackson Laboratory H2 Haplotype g7 Generation N2F3p+F2+F1p Appearance
albino, pink eyed
Related Genotype: A/A Tyrc/TyrcStrain Description
CD38 is an ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase. This ubiquitously expressed ectoenzyme is the major NAD hydrolase in mice. NOD/Lt mice homozygous for the Cd38tm1Lnd targeted allele develop accelerated Type 1 diabetes associated with an ART2 (T cell ADP-ribosyltransferase)-dependent and NAD-mediated loss of regulatory CD4+CD25+ Foxp3+ and CD4+iNKT cells (Chen, J. et al 2006; Chen, Y.G et al 2006). Combining the Prkdcscid mutation with the Cd38tm1Lnd targeted allele completely prevents diabetes development. For investigators wishing to study the role of CD38 in beta cell biology, the presence of the Prkdcscid allele provides insultis-free islets for analysis. Congenic, doubly homozygous NOD.Cd38tm1Lnd Prkdcscid mutant mice exhibit no significant difference in glucose tolerance when compared to NOD or NOD. Prkdcscid, thus not supporting a previous report(Okamoto, H. and S. Takasawa; 2002) that CD38 is required for normal pancreatic beta cell glucose responsiveness. NOD.Cg-Cd38tm1LndPrkdcscid/LtJ mice offer an alternative means for maintaining the targeted CD38 allele on the NOD background. Without the Prkdcscid mutation, the accelerated diabetogenesis produ ced by CD38 deficiency makes colony propagation difficult.Strain Development
NOD mice homozygous for the Cd38tm1Lnd allele (stock# 004311) were crossed to NOD.Prkdcscidmice for 2 generations, prior to making homozygous for scid and the CD38 targeted mutation. FACS analysis, of peripheral blood cells, confirms the absence of mature T and B cells and CD38 deficiency. In 2006, the T1DR received NOD.Cg- NOD.Cg-Cd38tm1LndPrkdcscid/Lt at generation [N2F3p].
Gene & Allele Details
| Allele Symbol | Cd38tm1Lnd | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Frances E Lund | ||
| Common Name(s) | CD38-; CD38null; | ||
| Mutation Made By | Debra Cockayne, Roche Bioscience | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14.1 | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Gene Symbol and Name | Cd38, CD38 antigen | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | CD38 antigen, related sequence 1; Cd38-rs1; T10; | ||
| Molecular Note | A neomycin selection cassette replaced a genomic fragment containing exons 2 and 3, which encode the putative active site of the encoded protein. Homozygous mice lacked transcripts derived from this allele (data not shown). Flow cytometry analysis on splenocytes derived from homozygous mice confirmed that no detectable protein was expressed on the cell surface. [MGI Ref ID J:49170] | ||
| 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] | ||
Control Information
| Control | ||
|---|---|---|
| 001303 NOD.CB17-Prkdcscid/J | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Prkdcscid
Related Strains
Strains carrying Cd38tm1Lnd allele
003727 B6.129P2-Cd38tm1Lnd/J 005347 NOD.129(B6)-Cd38tm1Lnd Art2atm1Fkn Art2btm1Fkn/Lt 004311 NOD.129P2(B6)-Cd38tm1Lnd/LtJ View Strains carrying Cd38tm1Lnd (3 strains)
Additional Web Information
Congenic Nomenclature
Research Applications
This mouse can be used to support research in many areas including:
Cd38tm1Lnd relatedDiabetes and Obesity Research
Islet Transplantation Studies
Type 1 Diabetes (IDDM) Analysis Strains (NOD Congenics with Mutations Affecting Immunocompetence)
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Research Tools
Immunology and Inflammation Research (B and T cell deficiency)
Immunology and Inflammation Research (T cell deficiency) (xenograft/transplant host)
Prkdcscid relatedCancer Research
Genes Regulating Growth and Proliferation
Diabetes and Obesity Research
Type 1 Diabetes (IDDM)
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Inflammation
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 ReferencesChen J; Chen YG; Reifsnyder PC; Schott WH; Lee CH; Osborne M; Scheuplein F; Haag F; Koch-Nolte F; Serreze DV; Leiter EH. 2006. Targeted disruption of CD38 accelerates autoimmune diabetes in NOD/Lt mice by enhancing autoimmunity in an ADP-ribosyltransferase 2-dependent fashion. J Immunol 176(8):4590-9. [PubMed: 16585549] [MGI Ref ID J:108097]
Price and Supply Information
| Strain Name: | NOD.Cg-Cd38tm1Lnd Prkdcscid/LtJ |
| Stock Number: | 005345 |
Price Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. 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. |
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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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