Overview

Also Known As:NSG DR4, NSG-DR4

NSG DR4 mice are NOD.scid.Il2Rγc^null ("NSG") animals with the DR4β(NT) transgene that encodes a human HLA-DRB1*0401 engineered to have amino acid mutations in the β2 domain for better interaction with murine CD4. The NSG platform is permissive for xenograft/human tumor growth, with the DR4β(NT) transgene allowing irradiated NSG DR4 mice to be engrafted with HLA-DR-matched hematopoietic stem cells (HSC) - resulting in humanized T cell and B cell populations.

Donating Investigator

Dr. Leonard D. Shultz, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Prkdc^scid

Allele Type	Gene Symbol	Gene Name
Spontaneous	Prkdc	protein kinase, DNA activated, catalytic polypeptide

Il2rg^tm1Wjl

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Il2rg	interleukin 2 receptor, gamma chain

Tg(H2-Ea-HLA-DRB10401)1Dv

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Virology Research
Cancer Research
Research Tools
Internal/Organ Research
Cardiovascular Research
Hematological 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

NSG DR4 mice are NOD.scid.Il2Rγc^null ("NSG"; Stock No. 005557) animals with the DR4β(NT) transgene that encodes a human HLA-DRB1*0401 modified to have improved interaction with murine CD4.
The presence of the DR4β(NT) transgene allows irradiated NSG DR4 mice to be engrafted with HLA-DR-matched hematopoietic stem cells (HSC) - resulting in humanized T cell and B cell populations.

Females that are homozygous for both mutations and homozygous for the DR4β(NT) transgene, and males that are homozygous for scid, hemizygous for the X-linked Il2Rγc^null mutation and homozygous for the DR4β(NT) transgene, may be collectively referred to as homozygous NSG DR4 mice.

Although viable and fertile, homozygous NSG DR4 mice are immunodeficient: they have no mature T cells or B cells, lack functional natural killer (NK) cells, have reduced numbers of lymphocytes and myeloid dendritic cells, and are deficient in cytokine signaling. The NSG platform is permissive for xenograft/human tumor growth.

The DR4β(NT) transgene has the mouse H2-Eα promoter directing expression of the HLA class II antigen binding domain molecule (HLA-DRB1*0401) modified to have amino acid mutations in the β2 domain for better interaction with murine CD4. In humans, the HLA-DR4 genotype (HLA-DRA/HLA-DRB1*0401) is associated with the development of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, type 1 diabetes, and lyme disease-induced arthritis.

Maintenance Note: Similar to other immunodeficient strains, maintaining homozygous NSG DR4 mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG DR4 animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.

View our
Resources for the NSG mouse model, including discussion forum, immunodeficient model comparison, and categorized, up-to-date references.

Development

NSG DR4 mice are NOD.scid.Il2Rγc^null ("NSG") animals with the DR4β(NT) transgene. Each mutation/transgene is described below.

NSG mice are non-obese diabetic animals (NOD/ShiLtJ) harboring the spontaneous severe combined immunodeficiency mutation (Prkdc^scid) on chromosome 16 and the Il2Rγc^null mutation at ~101 Mbp on the X chromosome (Il2rg^tm1Wjl created by Dr. Warren J. Leonard [NIH]). NSG mice are described and available from The Jackson Laboratory Repository as Stock No. 005557.

The DR4β(NT) transgene (also called DR4β(NT)/pDOI-5) was generated by Dr. Chella S. David (Mayo Clinic) as described in Pan et al. 1998 J Immunol 161:2925. This transgene has the mouse H2-Eα promoter (and rabbit β-globin intron) upstream of "DRB1*0401(NT)" - a human HLA-DRB1*0401 cDNA sequence engineered to have amino acid mutations (Q110N*K139T) in the β2 domain for better interaction with murine CD4. The transgene was microinjected into fertilized eggs from (SWR x B10)F1 mice. Mice from the founder line with five transgene copies were backcrossed to B10.RFB3 animals (C57BL/10-congenic Eβ⁰ Eα^p mice lacking endogenous Eβ but expressing Eα intracytoplasmically). Next, Dr. David backcrossed them to NOD inbred mice for five generations. In 2009, the NOD-congenic DR4 Ab⁰ mice were sent to Dr. Leonard D. Shultz (The Jackson Laboratory). They were then bred to NSG mice (Stock No. 005557) for at least one generation, and the Ab⁰ mutation was replaced with the endogenous H2-Ab1 allele.
The resulting NSG DR4 animals were bred together for several generations, and then made available as Stock No. 029295.

Expression Data

Expressed Gene	HLA-DRB1, major histocompatibility complex, class II, DR beta 1, human
Site of Expression

Control Suggestions

Wild-type from the colony

Approximate Controls

Depending upon the experiment, the following may be appropriate control strain(s):
--NOD.scid.IL2RγcKO ("NSG"; Stock No. 005557)
--NOD.scid (Stock No. 001303)
--NOD/ShiLtJ inbred mice (Stock No. 001976)
001303 NOD.Cg-Prkdc^scid/J
001976 NOD/ShiLtJ
005557 NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ

Additional Information

Considerations for Choosing Controls

Selected References

Pan S; Trejo T; Hansen J; Smart M; David CS. 1998. HLA-DR4 (DRB1*0401) transgenic mice expressing an altered CD4-binding site: specificity and magnitude of DR4-restricted T cell response. J Immunol 161(6):2925-9PubMed: 9743354 MGI: J:134781

View All References

Genetics

Prkdc^scid

Allele Symbol: Prkdc^scid

Allele Name	severe combined immunodeficiency
Allele Type	Spontaneous
Allele Synonym(s)	SCID
Gene Symbol and Name	Prkdc, protein kinase, DNA activated, catalytic polypeptide
Gene Synonym(s)
Site of Expression	T and B lymphocytes.
Strain of Origin	C.BKa-Igh^b/Icr
Chromosome	16
Molecular Note	A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*).

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Allele Name	targeted mutation 1, Warren J Leonard
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	[KO]gammac; CD132^-; gammac^-; gc^-; Il2rg^tm1Wjll; IL2Rgamma^null
Gene Symbol and Name	Il2rg, interleukin 2 receptor, gamma chain
Gene Synonym(s)
Site of Expression	Primarily lymphoid cells.
Strain of Origin	129S4/SvJae
Chromosome	X
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.
Mutations Made By	Dr. Warren Leonard, NHLBI, NIH

Tg(H2-Ea-HLA-DRB10401)1Dv

Allele Symbol: Tg(H2-Ea-HLA-DRB10401)1Dv

Allele Name	transgene insertion 1, Chella David
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	DR4beta(NT)
Gene Symbol and Name	Tg(H2-Ea-HLA-DRB10401)1Dv, transgene insertion 1, Chella David
Gene Synonym(s)
Promoter	H2-Ea, histocompatibility 2, class II antigen E alpha,
Expressed Gene	HLA-DRB1, major histocompatibility complex, class II, DR beta 1, human
Strain of Origin	(SWR x C57BL/10)F1
Chromosome	UN
Molecular Note	This transgene has the mouse H2-Ealpha promoter (and rabbit beta-globin intron) upstream of a human HLA-DRB1*0401 cDNA sequence engineered to have amino acid mutations (Q110N and K139T) in the beta2 domain to provide an improved interaction with murine CD4.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Prkdc^scid related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
Virology Research
- B and T Cell Deficiency
  - AIDS research tool
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

Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
- Immunodeficiency Associated with Other Defects
- Autoimmunity
  - specific complement deficiency
  - B and T cell deficiency
  - B cell deficiency
- Immunodeficiency
  - specific complement deficiency
  - T cell deficiency
  - multiple immune defects
  - Macrophage defects
  - B and T cell deficiency
  - NK Cell Deficiency
  - MHC class II defects
  - MHC class II deficient
  - NK Cell and Cd8 T Cell defects
  - defects in humoral immune responses
  - B cell defects
  - B cell deficiency
  - B, T, and NK cell deficiency
- T Cell Receptor Signaling Defects
  - B and T cell deficiency, xenograft/transplant host
  - B and T cell deficiency
- HLA transgenics
- Lymphoid Tissue Defects
  - B and T cell deficiency
  - hematopoietic development
- Graft vs. Host Disease
- Inflammation
  - B and T cell deficiency
- Growth Factors/Receptors/Cytokines
Internal/Organ Research
- Thymus Defects
  - B and T cell deficient
- Lymphoid Tissue Defects
  - T cell deficiency
  - B and T cell deficiency
Research Tools
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
  - T cell deficiency
  - production of B and T cells, antibodies, and hybridomas
  - genes regulating lymphoma development
  - xenograft/transplant host
  - production of T cells and hybridoma
  - B, T, and NK cell deficiency, xenograft/transplant host
  - production of B cells and antibodies
  - B cell deficiency
- Immunology, Inflammation and Autoimmunity Research
  - B and T cell deficiency
  - specific complement deficiency
  - Macrophage Deficiency
  - T cell deficiency
  - B, T, and NK cell deficiency
  - NK Cell Deficiency
  - MHC class II defects
  - genes regulating susceptibility to infectious disease and endotoxin
  - background strain for histocompatibility congenics
  - T cell deficiency, xenograft/transplant host
  - production of T cell lines and hybridomas
  - B cell deficiency
  - production of B cells and antibodies
  - production of B cells, antibodies T cell lines, and hybridomas
- Toxicology Research
  - xenograft/transplant host
  - B and T cell deficiency, xenograft transplant host
Virology Research
- B and T Cell Deficiency
  - AIDS research tool
Cardiovascular Research
- Vascular Defects
  - defective macrophage function
Cancer Research
- Toxicology
  - B and T cell deficiency, xenograft/transplant host
  - xenograft/transplant host
- Growth Factors/Receptors/Cytokines
Hematological Research
- Hematopoietic Defects
- Immunological Defects
  - B and T cell deficiency
Developmental Biology Research
- Lymphoid Tissue Defects
  - hematopoietic defects
- Internal/Organ Defects
  - hematopoietic defects
  - Lymphoid Tissue Defects

Genotype: Il2rg^tm1Wjl related

Cancer Research
- Growth Factors/Receptors/Cytokines
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines

Mammalian Phenotype Terms by Genotype

References

Pan S; Trejo T; Hansen J; Smart M; David CS. 1998. HLA-DR4 (DRB1*0401) transgenic mice expressing an altered CD4-binding site: specificity and magnitude of DR4-restricted T cell response. J Immunol 161(6):2925-9PubMed: 9743354 MGI: J:134781

Additional - Il2rg^tm1Wjl related

Additional - Prkdc^scid related

Additional - Tg(H2-Ea-HLA-DRB10401)1Dv related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- QPCR:Tg(HLA-A)-1
- QPCR:Tg(HLA-A)-1
- Standard PCR:Tg(HLA-A2/H2-D/B2m)
- Probe:Il2rg-PROBE
- Probe:Il2rg-PROBE
- End Point Analysis:Prkdc End Point
- QPCR:Tg(HLA-DRB1)Dmz-qPCR
- Standard PCR:Tg(HLA-DRB1) Alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

Females that are homozygous for both mutations and homozygous for the DR4β(NT) transgene, and males that are homozygous for scid (Prkdc^scid), hemizygous for the X-linked Il2Rγc^null mutation (Il2rg^tm1Wjl) and homozygous for the DR4β(NT) transgene, may be collectively referred to as homozygous NSG DR4 mice.

When maintaining a live colony, homozygous NSG DR4 females may be bred with homozygous NSG DR4 males.
Homozygous NSG DR4 mice are immunodeficient. As such, and similar to other immunodeficient strains, maintenance in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG DR4 animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health. Also see additional NSG housing information.
- Additional Breeding and Husbandry Support
Citation
When using the NSG DR4 mouse strain in a publication, please cite the originating article(s) and include JAX stock #029295 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
	Females will be Homozygous for Prkdc<scid> and Il2rg<tm1Wjl> and HemizygousTg(H2-Ea-HLA-DRB10401)1Dv. Males will be will be Homozygous for Prkdc<scid>, and Hemizygous for Il2rg<tm1Wjl> and Tg(H2-Ea-HLA-DRB10401)1Dv.

Payment Terms and Conditions

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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.

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General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Research institutions require an MTA, companies require a (no fee) commercial use agreement prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

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Also Known As:NSG DR4, NSG-DR4

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Prkdcscid

Allele Symbol: Prkdcscid

Il2rgtm1Wjl

Allele Symbol: Il2rgtm1Wjl

Tg(H2-Ea-HLA-DRB1*0401*)1Dv

Allele Symbol: Tg(H2-Ea-HLA-DRB1*0401*)1Dv

Disease Terms

Research Areas By Phenotype

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

Genotype: Prkdcscid related

Genotype: Il2rgtm1Wjl related

Mammalian Phenotype Terms by Genotype

References

Additional - Il2rgtm1Wjl related

Additional - Prkdcscid related

Additional - Tg(H2-Ea-HLA-DRB1*0401*)1Dv 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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Prkdc^scid

Allele Symbol: Prkdc^scid

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Tg(H2-Ea-HLA-DRB10401)1Dv

Allele Symbol: Tg(H2-Ea-HLA-DRB10401)1Dv

Genotype: Prkdc^scid related

Genotype: Il2rg^tm1Wjl related

Additional - Il2rg^tm1Wjl related

Additional - Prkdc^scid related

Additional - Tg(H2-Ea-HLA-DRB10401)1Dv related