Strain Name: |
NOD.129(B6)-Prkdcscid Iduatm1Clk/J |
|---|---|
Stock Number: |
004083 |
Availability: | Repository-Cryopreserved |
General Terms and Conditions |
| Former Name |
NOD.129(B6)-PrkdcscidIduatm1Clk/J (Changed: 23-NOV-05
) |
|
NOD.129(B6)-PrkdcscidIduatm1Clk (Changed: 15-DEC-04
) | |
| Genes & Alleles | Idua; Iduatm1Clk; 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 - Targeted Mutation Species laboratory mouse Donating Investigator Lorne Clarke, University of British Columbia Appearance
albino
Related Genotype: Tyrc/TyrcStrain Description
At birth, mice that are homozygous null for the Idua gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No alpha-L-iduronidase enzyme activity or mRNA is detected. By three weeks of age, homozygous null mice develop a flattened facial profile and a thickening of digits. Defective bone formation is noticeable by fifteen weeks, characterized by a broadening and thickening of long bones. Evidence of lysosomal storage disorder is apparent in cells of the reticuloendothelial system at four weeks. By eight weeks progressive evidence of lysosomal storage is seen in Kupffer cells, splenic sinusoidal lining cells, chondrocytes, glial and Purkinje cells. This animal model is suitable for use in studies investigating the lysosomal storage disorder mucopolysaccharidosis type I (MPS I).Strain Development
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt exon 5 of the Idua gene. The construct was introduced into 129X1/SvJ X 129S1/Sv-derived R1 embryonic stem (ES) cells. Care was taken not to disrupt the closely linked Sfat sulfate transporter gene. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
Gene & Allele Details
| Allele Symbol | Iduatm1Clk | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Lorne A Clarke | ||
| Mutation Made By | Lorne Clarke, University of British Columbia | ||
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| ES Cell Line Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| Gene Symbol and Name | Idua, iduronidase, alpha-L- | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | IDA; MPS1; | ||
| Molecular Note | A neomycin selection cassette was inserted into exon 6. RT-PCR analysis on RNA derived from liver and kidney of homozygous mice demonstrated that no detectable transcript was produced from this allele. Enzymatic activity assays on homogenates of liver,kidney, brain and tail clippings of homozygous mice confirmed that no functional protein was expressed from this allele. [MGI Ref ID J:39522] | ||
| 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
| Allele | Control | |
|---|---|---|
| Iduatm1Clk | Wild-type from the colony | |
| Prkdcscid | None Available | |
| Considerations for Choosing Controls | ||
Genotyping Protocols
Iduatm1Clk
Prkdcscid
Colony Maintenance
| Breeding & Husbandry | These mice arose on a B6;129 background and have been backcrossed to NOD-Prkdcscidmice for at least 12 generations.Coat color expected from breeding:Albino When maintained in a live colony, mating scheme is (-/-)(+/+) x (-/-)(+/-). |
|---|---|
| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
Strains carrying Iduatm1Clk allele
004068 B6.129-Iduatm1Clk/J View Strains carrying Iduatm1Clk (1 strain)
Additional Web Information
Congenic Nomenclature
Research Applications
This mouse can be used to support research in many areas including:Iduatm1Clk related
Prkdcscid relatedDevelopmental Biology Research
Skeletal Defects
Internal/Organ Research
Heart Abnormalities
Liver Defects
Lymphoid Tissue Defects
Spleen Defects
Metabolism Research
Neurobiology Research
Cerebellar Defects
Metabolic 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
Selected Reference(s)
Additional ReferencesClarke LA; Russell CS; Pownall S; Warrington CL; Borowski A; Dimmick JE ; Toone J ; Jirik FR. 1997. Murine mucopolysaccharidosis type I: targeted disruption of the murine alpha-L-iduronidase gene. Hum Mol Genet 6(4):503-11. [PubMed: 9097952] [MGI Ref ID J:39522]
Price and Supply Information
| Strain Name: | NOD.129(B6)-Prkdcscid Iduatm1Clk/J |
| Stock Number: | 004083 |
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 for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. |
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
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