Overview

Also Known As:NOD/LtSz-Rag1nullPfpnull

These double knock-out mutant mice have no mature T or B lymphocytes, no detectable NK cell cytotoxic activity, and lack serum immunoglobulin. They also develop thymic lymphomas.

Donating Investigator

Dr. Leonard D. Shultz, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Prf1^tm1Sdz

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Prf1	perforin 1 (pore forming protein)

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Rag1	recombination activating gene 1

Research Applications

Research Tools
Hematological Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Cancer Research
Apoptosis Research
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Mice that are homozygous for both targeted mutations are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities when housed under specific pathogen free conditions. These double homozygote mutant mice have no mature T or B lymphocytes, no detectable NK cell cytotoxic activity, and lack serum immunoglobulin. The number of nucleated spleen cells is significantly reduced in double mutant mice, when compared to the single homozygote, NOD.129S7(B6)-Rag1^tm1Mom/J (Stock No. 003729). Although an increased number of DX5⁺CD122⁺ NK cells are found in the spleens of double mutants, these NK cells have impaired cytotoxic activity. The disruption of Prf1 ablates NK cell cytotoxic activity resulting in increased engraftment levels over that observed with Stock No. 003729. All mutant mice develop thymic lymphomas. This double mutant mouse strain may be useful in studies involving engraftment of human hematolymphoid cells.

Development

Please see strain entries Stock No. 002407 and Stock No. 003729 for details regarding the construction of each mutant allele. This strain was produced by crossing female NOD.129S7(B6)-Rag1^tm1Mom/J (Stock No. 003729) to male C57BL/6-Prf1^tm1Sdz (Stock No. 002407). Resulting female progeny heterozygous for both mutant alleles were crossed to male NOD.129S7(B6)-Rag1^tm1Mom/J (Stock No. 003729). Mice homozygous for the Rag1 mutant allele and heterozygous for the Prf1 allele were crossed to NOD.129S7(B6)-Rag1^tm1Mom/J (Stock No. 003729) mice for 10 generations, and then intercrossed to produce double homozygotes.

Control Suggestions

Approximate Controls

001976 NOD/ShiLtJ

Additional Information

Considerations for Choosing Controls

Selected References

Shultz LD; Banuelos S; Lyons B; Samuels R; Burzenski L; Gott B; Lang P; Leif J; Appel M; Rossini A; Greiner DL. 2003. NOD/LtSz-Rag1nullPfpnull mice: a new model system with increased levels of human peripheral leukocyte and hematopoietic stem-cell engraftment. Transplantation 76(7):1036-42PubMed: 14557749 MGI: J:109843

View All References

Genetics

Prf1^tm1Sdz

Allele Symbol: Prf1^tm1Sdz

Allele Name	targeted mutation 1, Sandoz Pharmaceuticals
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	P⁰; perf-; perforin-; perforin 0; Pfn^-; pfp-; Pfp^tm1Sdz; pfpKO; pko; Prf^-; Prf1^-; Prf1^tm/Sdz; prf1^tm1
Gene Symbol and Name	Prf1, perforin 1 (pore forming protein)
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	10
Molecular Note	A neomycin selection cassette was inserted into exon 3. RT-PCR analysis on RNA derived from homozygous mice demonstrated that an abnormal transcript was produced from this allele. However, immunocytochemistry experiments on activated spleen cells derived from homozygous mice confirmed that no detectable protein was made from this allele.
Mutations Made By	Dr. Birgit Lederman, University of Zurich

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Allele Name	targeted mutation 1, Peter Mombaerts
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Rag-; Rag^1tm1Mom; RAG-1-; Rag1^-; RAG1^null; Rag-1KO
Gene Symbol and Name	Rag1, recombination activating gene 1
Gene Synonym(s)
Site of Expression	expression is seen in bone marrow derived cell lines.
Strain of Origin	129S7/SvEvBrd-Hprt⁺
Chromosome	2
Molecular Note	A 1356 bp genomic fragment of the Rag1 gene, encoding the nuclear localization signal and the zinc-finger motif, was replaced by a neomycin cassette. A mutant transcript expressed from this allele was detected by Northern blot in bone marrow derived cell lines from homozygous mice.
Mutations Made By	Peter Mombaerts, Max Planck Research Unit for Neurogenetics

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Research Tools
- Cancer Research
  - B cell deficiency
  - T cell deficiency
  - genes regulating lymphoma development
  - production of B and T cells, antibodies, and hybridomas
  - xenograft/transplant host
  - B and T cell deficiency, xenograft/transplant host
  - B, T, and NK cell deficiency, xenograft/transplant host
- Immunology, Inflammation and Autoimmunity Research
  - B and T cell deficiency
  - T cell deficiency
  - B cell deficiency
  - B, T, and NK cell deficiency
  - NK Cell Deficiency
  - production of B cells, antibodies T cell lines, and hybridomas
  - production of T cell lines and hybridomas
  - T cell deficiency, xenograft/transplant host
- Toxicology Research
  - B and T cell deficiency, xenograft transplant host
  - xenograft/transplant host
Internal/Organ Research
- Lymphoid Tissue Defects
  - T cell deficiency
  - B and T cell deficiency
- Thymus Defects
  - B and T cell deficient
Immunology, Inflammation and Autoimmunity Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
  - hematopoietic development
- Immunodeficiency
  - B and T cell deficiency
  - B cell deficiency
  - B, T, and NK cell deficiency
  - multiple immune defects
  - NK Cell Deficiency
- Inflammation
  - B and T cell deficiency
- Autoimmunity
  - B and T cell deficiency
  - B cell deficiency
Cancer Research
- Increased Tumor Incidence
  - Lymphomas
  - Lymphomas: thymic
- Toxicology
  - B and T cell deficiency, xenograft/transplant host
Hematological Research
- Immunological Defects
  - B and T cell deficiency
Developmental Biology Research
- Lymphoid Tissue Defects
  - hematopoietic defects

Genotype: Rag1^tm1Mom related

Hematological Research
- Immunological Defects
  - B and T cell deficiency
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
- T Cell Receptor Signaling Defects
  - B and T cell deficiency
- Inflammation
  - B and T cell deficiency
Research Tools
- Toxicology Research
  - xenograft/transplant host
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
Cancer Research
- Toxicology
  - B and T cell deficiency, xenograft/transplant host

Genotype: Prf1^tm1Sdz related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency Associated with Other Defects
Apoptosis Research
- Extracellular Modulators

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz Rag1^tm1Mom/Rag1^tm1Mom
NOD.Cg-Rag1 Prf1/SzJ

homeostasis/metabolism phenotype

increased circulating glucose level
- 70% of streptozotocin-treated mice transplanted with islet cells from Prkdc^scid/Prkdc^scid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice and HLA-A2 negative human peripheral blood mononuclear cells exhibit increased glucose serum levels
- els
- Normal - however, all of streptozotocin-treated mice transplanted with islet cells from Prkdc^scid/Prkdc^scid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice and HLA-A2 positive human peripheral blood mononuclear cells exhibit euglycemia
- streptozotocin-treated mice exhibit increased serum glucose levels that can be restored transiently to euglycemia by transplanting islet cells from Prkdc^scid/Prkdc^scid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice

immune system phenotype

abnormal response to transplant
- streptozotocin-treated mice transplanted with islet cells from Prkdc^scid/Prkdc^scid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice and HLA-A2 negative human peripheral blood mononuclear cells exhibit destruction of engrafted islet cells
- ls

Genotype: Rag1^tm1Mom/Rag1^tm1Mom Prf1^tm1Sdz/Prf1^tm1Sdz
NOD.Cg-Rag1 Prf1/Sz

immune system phenotype

abnormal thymus cortex morphology
- thymus lacks a clearly defined cortex

impaired natural killer cell mediated cytotoxicity
- poly I:C stimulated spleen cells exhibit extremely low levels of NK cell cyotoxic activity

increased immature B cell number
- IgLkappa- B220+ immature B cells are increased six-fold as compared to NOD controls

increased macrophage cell number
- numbers of macrophages are increased in comparison to NOD controls

abnormal lymph node cortex morphology
- lymph nodes lack follicles

decreased mature B cell number
- spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells

increased granulocyte number
- numbers of granulocytes are increased in comparison to NOD controls, however, in comparison to NOD-Rag^null numbers are decreased

spleen hypoplasia
- nucleated spleen cells are reduced 14 fold in 8-11 week old mice as compared to NOD control

abnormal level of surface class II molecules
- four to five-fold decrease in cells expressing I-A^g7 as compared to NOD control

thymus hypoplasia
- lymphoid cells are severely reduced in thymuses

abnormal response to transplant
- 6-8 weeks after IP injection, bone marrow exhibits a 12-fold increase in engraftment of human cord blood cells
- peripheral blood has a 13-fold increase in engraftment of human CD4+ T cells
- following IP injection of human PMBC, peripheral blood has a fivefold increase in the percentage of human lymphoid cells as compared to NOD-Rag^null controls
- spleens have a 9-fold increase in engraftment of human CD45+ cells and a 20-fold increase in human CD4+ cells as compared to control, although there is no significant difference in engraftment of human CD8+ cells

decreased CD8-positive, alpha-beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells

increased NK cell number
- numbers of NK cells are increased in comparison to NOD controls

abnormal spleen white pulp morphology
- spleen lacks lymphoid follicles

decreased immunoglobulin level
- no serum immunoglobulin is detected in 176-362 day old mice

decreased CD4-positive, alpha beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells

endocrine/exocrine gland phenotype

thymus hypoplasia
- lymphoid cells are severely reduced in thymuses

abnormal thymus cortex morphology
- thymus lacks a clearly defined cortex

increased T cell derived lymphoma incidence

mortality/aging

premature death
- mean lifespan is 262+/-21 days

neoplasm

increased T cell derived lymphoma incidence

hematopoietic system phenotype

decreased immunoglobulin level
- no serum immunoglobulin is detected in 176-362 day old mice

impaired natural killer cell mediated cytotoxicity
- poly I:C stimulated spleen cells exhibit extremely low levels of NK cell cyotoxic activity

spleen hypoplasia
- nucleated spleen cells are reduced 14 fold in 8-11 week old mice as compared to NOD control

abnormal spleen white pulp morphology
- spleen lacks lymphoid follicles

increased macrophage cell number
- numbers of macrophages are increased in comparison to NOD controls

decreased mature B cell number
- spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells

decreased CD4-positive, alpha beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells

increased granulocyte number
- numbers of granulocytes are increased in comparison to NOD controls, however, in comparison to NOD-Rag^null numbers are decreased

abnormal thymus cortex morphology
- thymus lacks a clearly defined cortex

increased immature B cell number
- IgLkappa- B220+ immature B cells are increased six-fold as compared to NOD controls

thymus hypoplasia
- lymphoid cells are severely reduced in thymuses

decreased CD8-positive, alpha-beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells

increased NK cell number
- numbers of NK cells are increased in comparison to NOD controls

References

Shultz LD; Banuelos S; Lyons B; Samuels R; Burzenski L; Gott B; Lang P; Leif J; Appel M; Rossini A; Greiner DL. 2003. NOD/LtSz-Rag1nullPfpnull mice: a new model system with increased levels of human peripheral leukocyte and hematopoietic stem-cell engraftment. Transplantation 76(7):1036-42PubMed: 14557749 MGI: J:109843

Additional - Prf1^tm1Sdz related

Additional - Rag1^tm1Mom related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Prf1
- Standard PCR:Prf1
- Standard PCR:Rag1Alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

This strain is maintained as a homozygote for both mutant alleles, under specific pathogen free conditions.
- Additional Breeding and Husbandry Support
Citation
When using the NOD/LtSz-Rag1nullPfpnull mouse strain in a publication, please cite the originating article(s) and include JAX stock #004848 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Homozygous for Rag1<tm1Mom> Homozygous for Prf1<tm1Sdz>, 1 pair minimum

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:NOD/LtSz-Rag1nullPfpnull

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Prf1tm1Sdz

Allele Symbol: Prf1tm1Sdz

Rag1tm1Mom

Allele Symbol: Rag1tm1Mom

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Rag1tm1Mom related

Genotype: Prf1tm1Sdz related

Mammalian Phenotype Terms by Genotype

Genotype: Prf1tm1Sdz/Prf1tm1Sdz Rag1tm1Mom/Rag1tm1MomNOD.Cg-Rag1 Prf1/SzJ

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Rag1tm1Mom/Rag1tm1Mom Prf1tm1Sdz/Prf1tm1SdzNOD.Cg-Rag1 Prf1/Sz

immune system phenotype

endocrine/exocrine gland phenotype

mortality/aging

neoplasm

hematopoietic system phenotype

References

Additional - Prf1tm1Sdz related

Additional - Rag1tm1Mom related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Prf1^tm1Sdz

Allele Symbol: Prf1^tm1Sdz

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Genotype: Rag1^tm1Mom related

Genotype: Prf1^tm1Sdz related

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz Rag1^tm1Mom/Rag1^tm1Mom
NOD.Cg-Rag1 Prf1/SzJ

Genotype: Rag1^tm1Mom/Rag1^tm1Mom Prf1^tm1Sdz/Prf1^tm1Sdz
NOD.Cg-Rag1 Prf1/Sz

Additional - Prf1^tm1Sdz related

Additional - Rag1^tm1Mom related