Strain Name: |
NOD.Cg-Prkdcscid Tg(Ins2-CD86)12B70Flv/FswJ |
|---|---|
Stock Number: |
007840 |
Availability: | Repository- Live |
General Terms and Conditions |
| Strain Common Names | NOD.RIP-CD86; |
| Genes & Alleles | CD86; Ins2; Prkdc; Prkdcscid; Tg(Ins2-CD86)12B70Flv; |
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 - Transgenic Mating System Noncarrier x Hemizygote (Female x Male) Species laboratory mouse Background Strain NOD Donor Strain (B6XCBA/Ca)F2 Donating Investigator F. Wong, University of Bristol H2 Haplotype g7 Generation N14F?+N1F0 (07-MAR-08) Appearance
Albino
Related Genotype: A/A Tyrc/TyrcStrain Description
Tg(Ins2-CD86)12B7 mice homozygous for the Prkdcscid mutation are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Transgenic mice express the human CD86 T cell co-stimulatory protein under the control of the rat insulin promoter (Ins2). RT-PCR analysis detects human CD86 mRNA expression in the pancreas. Very low expression levels are also detected in the kidney and thymus of some but not all transgenic mice. Immunohistochemistry indicates that transgenic CD86 protein expression is restricted to the Islets of Langerhans. Transgenic, Prkdcscid homozygous mice lack functional T cells and B cells, and do not become diabetic.In the absence of the Prkdcscid mutation, NOD-Tg(Ins2-CD86), transgenic mice experience accelerated diabetes. Diabetes onset in male and female transgenic NOD-Tg(Ins2-CD86) mice starts at 8 weeks of age and 85-90% of the mice ultimately become diabetic. Disease progression, however, is not as rapid as in congenic NOD-Tg(Ins2-CD80) transgenic mice.. Both CD80 and CD86 cause accelerated diabetes on the NOD background but there appeared to be a "stronger" effect of CD80. Paradoxically, however, when cells from both diabetic transgenic strains are used in adoptive transfer, the cells from the more accelerated diabetic Tg(Ins2-CD80) stock are far less able to adoptively transfer diabetes to the host than are those from the slower, but still accelerated, Tg(Ins2-CD86) diabetic stock.
In contrast with NOD-Tg(Ins2-CD86) transgenic mice, congenic C57BL/6-Tg(Ins2-CD86) transgenic mice develop perivascular/periductal infiltrations starting around 7-8 months of age, but do not develop insulitis or diabetes.
These Prkdcscid homozygous Tg(Ins2-CD86) hemizyous mice are useful for adoptive transfer experiments and as a source of insulitis free pancreatic islets.
Strain Development
A transgenic construct containing the human CD86 gene driven by the rat insulin promoter (RIP) was injected into fertilized (C57BL/6XCBA/Ca)F2 embryos. Founder animals were initially bred to C57BL/6. Resulting progeny of founder 12B70 were backcrossed to NOD for 14 generations prior to mating to NOD.CB17-Prkdcscid mice. In 2007, The Jackson Laboratory received this mice homozygous for the Prkdcscid mutation and Tg/? at generation N14F?. The Jackson Laboratory backcrossed the mice received with NOD.CB17-Prkdcscid/J (Stock No. 001303) prior to sibling mating.
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-CD86)12B70Flv | ||
| Allele Name | transgene insertion 12B70, Richard Flavell | ||
| Common Name(s) | RIP-CD86; | ||
| Mutation Made By | Richard Flavell, Yale University School of Medicine | ||
| Strain of Origin | (C57BL/6 x CBA/Ca)F2 | ||
| Expressed Gene | CD86, CD86 molecule, human | ||
| Promoter | Ins2, insulin 2, rat | ||
| Molecular Note | The transgenic construct contains the human CD86 gene driven by the rat insulin 2 promoter (RIP). Transgenic protein expression is restricted to the Islets of Langerhans. [MGI Ref ID J:93555] | ||
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 001303 NOD.CB17-Prkdcscid/J | (approximate) | |
| 001976 NOD/ShiLtJ | (approximate) | |
| Considerations for Choosing Controls | ||
Genotyping Protocols
Prkdcscid
Tg(Ins2-CD86)12B70Flv
Colony Maintenance
| Diet Information | LabDiet® 5K52/5K67 |
|---|
Related Strains
Strains carrying Prkdcscid allele
View Strains carrying Prkdcscid (25 strains)
Additional Web Information
Congenic Nomenclature
Animal Health Reports
Room Number AX12
Research Applications
This mouse can be used to support research in many areas including:
Prkdcscid relatedDiabetes and Obesity Research
Islet Transplantation Studies
Type 1 Diabetes (IDDM) Analysis Strains (NOD Congenics with Mutations Affecting Immunocompetence)
Type 1 Diabetes (IDDM) Analysis Strains (NOD Transgenics)
Immunology and Inflammation Research
T Cell Receptor Signaling Defects (B and T cell deficiency) (xenograft/transplant host)
Research Tools
Immunology and Inflammation Research (T cell deficiency) (xenograft/transplant host)
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 ReferencesGuerder S; Eynon EE; Flavell RA. 1998. Autoimmunity without diabetes in transgenic mice expressing beta cell-specific CD86, but not CD80: parameters that trigger progression to diabetes. J Immunol 161(5):2128-40. [PubMed: 9725204] [MGI Ref ID J:93555]
Price and Supply Information
| Strain Name: | NOD.Cg-Prkdcscid Tg(Ins2-CD86)12B70Flv/FswJ |
| Stock Number: | 007840 |
Price Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
Usually shipped between four and eight weeks of age. This strain is included in the Type 1 Diabetes Repository collection. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. |
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