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.
Dr. Leonard D. Shultz, The Jackson Laboratory
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous | Prkdc | protein kinase, DNA activated, catalytic polypeptide |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Il2rg | interleukin 2 receptor, gamma chain |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | H2-Ab1 | histocompatibility 2, class II antigen A, beta 1 |
Allele Type |
---|
Transgenic (Inserted expressed sequence, Humanized sequence) |
NSG-HLA-DQ8 mice are NOD.scid.Il2Rγcnull ("NSG") animals also harboring the H2-Ab1 knock-out allele (Abo) 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 Abo, homozygous for HLA-DQ8A and hemizygous for the X-linked Il2Rγcnull 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.
NSG-HLA-DQ8 mice (Stock No. 026561) are NOD.scid.Il2Rγcnull ("NSG") animals with the H2-Ab1 knock-out allele (Abo; 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 (Prkdcscid) on chromosome 16 and the Il2Rγcnull mutation on the X chromosome (Il2rgtm1Wjl 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-Ab1tm1Gru (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-Ab1tm1Doi 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 Abo 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-Abo; Stock No. 021885). The resulting NSG-Abo HLA-DQ8A mice, called NSG-HLA-DQ8, are available as Stock No. 026561.
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 |
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-Ighb/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*). |
Allele Name | targeted mutation 1, Warren J Leonard |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | [KO]gammac; CD132-; gammac-; gc-; Il2rgtm1Wjll; IL2Rgammanull |
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 |
Allele Name | targeted mutation 1, Christophe Benoist and Diane Mathis |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | A beta0; Abbeta-; AB0; Abeta-; Class II0; H2-Ab1tm1Dim; 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 |
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-DQA1*0301/DQB1*0302; Tg(HLA-DQA1*301,HLA-DQB1*302)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-H2f)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-Ab1tm1Dim 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-Ab1tm1Dim 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-DQA1*0301 gene and a promoter-truncated HLA-DQB1*0302 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 |
NSG-HLA-DQ8 females homozygous for all three mutations and homozygous for the HLA-DQ8A transgene, and males homozygous for scid (Prkdcscid), homozygous for Abo (H2-Ab1tm1Doi), homozygous for HLA-DQ8A (Tg(HLA-DQA1,HLA-DQB1)1Dv) and hemizygous for the X-linked Il2Rγcnull (Il2rgtm1Wjl) 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.
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.
Facility Barrier Level Descriptions
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 |
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 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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.