Overview

Also Known As:NSG-HLA-DQ8

NSG-HLA-DQ8 mice lack murine MHC class II and express mutant human leukocyte antigen (HLA)-DQ8 on the immunodeficient NOD scid gamma (NSG) background. This strain may be useful in studies utilizing an autoantigen-specific vaccination approach for the prevention of islet autoimmunity in individuals susceptible to type I diabetes.

Donating Investigator

Dr. Leonard D. Shultz, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Tg(HLA-DQA1,HLA-DQB1)1Dv

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

H2-Ab1^tm1Doi

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	H2-Ab1	histocompatibility 2, class II antigen A, beta 1

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

View Genetics

Research Applications

Research Tools
Internal/Organ Research
Immunology, Inflammation and Autoimmunity Research
Virology Research
Diabetes and Obesity Research
Cancer Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

NSG-HLA-DQ8 mice are NOD.scid.Il2Rγc^null ("NSG") animals also harboring the H2-Ab1 knock-out allele (Ab^o) and the human leukocyte antigen DQ8A transgene (HLA-DQ8A).

NSG-HLA-DQ8 females homozygous for all three mutations and homozygous for the HLA-DQ8A transgene, and males homozygous for scid, homozygous for Ab^o, homozygous for HLA-DQ8A and hemizygous for the X-linked Il2Rγc^null may be collectively referred to as homozygous NSG-HLA-DQ8 mice.

Homozygous NSG-HLA-DQ8 express HLA-DQ8 and lack murine MHC class II, on an NSG background (see Stock No. 005557 for NSG mouse description). Homozygous NSG-HLA-DQ8 mice are viable and fertile. Human haematopoietic stem cell-engraftment in NSG-HLA-DQ8 mice results in human insulin-specific Foxp3⁺ Treg-induction upon subimmunogenic vaccination with strong agonistic insulin mimetopes in vivo. These Tregs are stable and show increased expression of Treg signature genes while suppressing effector T cells.

Development

NSG-HLA-DQ8 mice (Stock No. 026561) are NOD.scid.Il2Rγc^null ("NSG") animals with the H2-Ab1 knock-out allele (Ab^o; see below) and the HLA-DQ8A transgene. NSG-HLA-DQ8 mice harbor several mutations, as 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 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 H2-Ab1 knock-out allele in Stock No. 026561 was originally reported to be H2-Ab1^tm1Gru (created by Dr. Michael J. Grusby; while at Harvard) - harboring a forward-oriented neomycin resistance cassette that disrupts H2-Ab1 exon 2 (and made in ES cells with a deletion in the promoter region of H2-Ea). In 2018, quality control efforts at The Jackson Laboratory were completed that revealed Stock No. 026561 instead has the very similar H2-Ab1^tm1Doi knock-out allele (created by Drs. Christophe Benoist and Diane Mathis; while at INSERM) - harboring a reverse-oriented neomycin resistance cassette that disrupts H2-Ab1 exon 2 (and made in ES cells with a deletion in the promoter region of H2-Ea). The Ab^o knock-out allele is on chromosome 17.

The HLA-DQ8A transgene (Tg(HLA-DQA1,HLA-DQB1)1Dv) was created by Dr. Chella David (Mayo Clinic). A 30kb DNA fragment containing the DQA*0301 gene from cosmid H11A and a 38kb DNA fragment containing the DQB*0302 gene from cosmid X10A were microinjected into (CBA/J x B10.M)F2 embryos. To establish germline transmission, founders were mated to the B10.M strain. Next, HLA-DQ8A transgenic mice were mated to NSG mice (Stock No. 005557) for at least ten generations. Subsequently, they were intercrossed with NSG mice lacking mouse MHC class II (NSG-Ab^o; Stock No. 021885). The resulting NSG-Ab^o HLA-DQ8A mice, called NSG-HLA-DQ8, are available as Stock No. 026561.

Expression Data

Expressed Gene	HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, human
Expressed Gene	HLA-DQB1, major histocompatibility complex, class II, DQ beta 1, human
Site of Expression
Site of Expression
Site of Expression	T and B lymphocytes.
Site of Expression	Primarily lymphoid cells.

Control Suggestions

Approximate Controls

Stock No. 021885
005557 NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ

Additional Information

Considerations for Choosing Controls

Selected References

Serr I; Furst RW; Achenbach P; Scherm MG; Gokmen F; Haupt F; Sedlmeier EM; Knopff A; Shultz L; Willis RA; Ziegler AG; Daniel C. 2016. Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice. Nat Commun 7:10991PubMed: 26975663 MGI: J:232395

View All References

Genetics

Tg(HLA-DQA1,HLA-DQB1)1Dv

Allele Symbol: Tg(HLA-DQA1,HLA-DQB1)1Dv

Allele Name	transgene insertion 1, Chella David
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	Abeta⁰.DQ8; DQ8; HLA-DQ8; HLA-DQ8 Tg; HLA-DQA10301/DQB10302; Tg(HLA-DQA1301,HLA-DQB1302)1Dv
Gene Symbol and Name	Tg(HLA-DQA1,HLA-DQB1)1Dv, transgene insertion 1, Chella David
Gene Synonym(s)
Promoter	HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, human
Promoter	HLA-DQB1, major histocompatibility complex, class II, DQ beta 1, human
Expressed Gene	HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, human
Expressed Gene	HLA-DQB1, major histocompatibility complex, class II, DQ beta 1, human
Strain of Origin	(CBA/J x B10.M-H2^f)F2
Chromosome	UN
General Note	Flow cytometric analysis of peripheral blood leukocytes (PBL) using a monoclonal antibody to HLA-DQ demonstrated that transgenic mice express the transgenes. 25-40% of the PBLs of mixed-background transgenic mice homozygous for the targeted MHC class II mutation H2-Ab1^tm1Dim express the transgenes. Lymph nodes of such mice contain three-fold the levels of CD4⁺ CD44⁺ T-cells as do those of nontransgenic MHC class II-deficient mice, levels similar to those of class II-sufficient mice. Immunization of transgenic H2-Ab1^tm1Dim homozygous mice with bovine collagen II results in a strong IgG antibody response to the immunogen, and 66% of these mice develop severe, persistent arthritis. (J:88296)
Molecular Note	A 30-kb human genomic DNA fragment containing the entire HLA-DQA10301 gene and a promoter-truncated HLA-DQB10302 gene from cosmid H11A and a 38-kb DNA fragment containing the entire HLA-DQB1*0302 gene from cosmid X10A were coinjected.
Mutations Made By	Chella David, Mayo Clinic

H2-Ab1^tm1Doi

Allele Symbol: H2-Ab1^tm1Doi

Allele Name	targeted mutation 1, Christophe Benoist and Diane Mathis
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	A beta⁰; A^bbeta^-; AB0; Abeta-; Class II⁰; H2-Ab1^tm1Dim; H2-Ab1tm1Doi; II⁰; MHC class II-; MHCII^-; MHC-II-k.o.
Gene Symbol and Name	H2-Ab1, histocompatibility 2, class II antigen A, beta 1
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	17
Molecular Note	The second exon was disrupted by the insertion of a neomycin resistance gene. In addition, the ES cell line used was derived from the 129S2/SvPas strain, which carries a deletion in the promoter region of H2-Ea. Consequently, these MHC class II molecule-deficient mice lacked cell surface expression of both class II-A and class II-E MHC proteins.
Mutations Made By	Christophe Benoist, Joslin Diabetes Center

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

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Prkdc^scid related

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
- Immunodeficiency
  - B and T cell deficiency
Virology Research
- B and T Cell Deficiency
  - AIDS research tool

Diabetes and Obesity Research
- Type 1 Diabetes (IDDM)
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - Type 1 Diabetes
- Immunodeficiency
  - MHC class II deficient
- Vaccine Development

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

Serr I; Furst RW; Achenbach P; Scherm MG; Gokmen F; Haupt F; Sedlmeier EM; Knopff A; Shultz L; Willis RA; Ziegler AG; Daniel C. 2016. Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice. Nat Commun 7:10991PubMed: 26975663 MGI: J:232395

Additional - H2-Ab1^tm1Doi related

Additional - Il2rg^tm1Wjl related

Additional - Prkdc^scid related

Additional - Tg(HLA-DQA1,HLA-DQB1)1Dv related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:H2-Ab1-Alternate 1
- Probe:Il2rg-PROBE
- End Point Analysis:Prkdc End Point
- QPCR:DQ8 Alpha
- QPCR:DQ8 Beta
- Separated PCR:H2-Ab1alternate2
- Standard PCR:Tg(HLA-DQA1)
- Standard PCR:Tg(HLA-DQB1)
- Genotyping resources and troubleshooting
Breeding Considerations

NSG-HLA-DQ8 females homozygous for all three mutations and homozygous for the HLA-DQ8A transgene, and males homozygous for scid (Prkdc^scid), homozygous for Ab^o (H2-Ab1^tm1Doi), homozygous for HLA-DQ8A (Tg(HLA-DQA1,HLA-DQB1)1Dv) and hemizygous for the X-linked Il2Rγc^null (Il2rg^tm1Wjl) may be collectively referred to as homozygous NSG-HLA-DQ8 mice.

When maintaining a live colony, homozygous NSG-HLA-DQ8 females may be bred with homozygous NSG-HLA-DQ8 males.
- Additional Breeding and Husbandry Support
Citation
When using the NSG-HLA-DQ8 mouse strain in a publication, please cite the originating article(s) and include JAX stock #026561 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 - Not-For-Profit & Academic Pricing

Service/Product	Description	Price
	Females will be homozygous for Prkdc<scid> , H2-Ab1<tm1Gru> and Il2rg<tm1Wjl> and homzygous or hemizygous for Tg(HLA-DQA1,HLA-DQB1)1Dv. Males will be homozygous for Prkdc<scid> and H2-Ab1<tm1Gru>, Hemizygous for Il2rg<tm1Wjl> and Homozygous or hemizygous for Tg(HLA-DQA1,HLA-DQB1)1Dv

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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. 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

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Also Known As:NSG-HLA-DQ8

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tg(HLA-DQA1,HLA-DQB1)1Dv

Allele Symbol: Tg(HLA-DQA1,HLA-DQB1)1Dv

H2-Ab1tm1Doi

Allele Symbol: H2-Ab1tm1Doi

Prkdcscid

Allele Symbol: Prkdcscid

Il2rgtm1Wjl

Allele Symbol: Il2rgtm1Wjl

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 - H2-Ab1tm1Doi related

Additional - Il2rgtm1Wjl related

Additional - Prkdcscid related

Additional - Tg(HLA-DQA1,HLA-DQB1)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 - Not-For-Profit & Academic 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

H2-Ab1^tm1Doi

Allele Symbol: H2-Ab1^tm1Doi

Prkdc^scid

Allele Symbol: Prkdc^scid

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Genotype: Prkdc^scid related

Genotype: Il2rg^tm1Wjl related

Additional - H2-Ab1^tm1Doi related

Additional - Il2rg^tm1Wjl related

Additional - Prkdc^scid related