NSG-Abo DR4 mice are NOD.scid.Il2Rγcnull ("NSG") animals with a murine major histocompatibility complex (MHC) class II knock-out allele (Abo) and 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. Homozygous Abo mice do not express murine MHC class II. The DR4β(NT) transgene allows irradiated NSG-Abo DR4 mice to be engrafted with HLA-DR-matched hematopoietic stem cells (HSC) - resulting in humanized T cell and B cell populations.
Dr. Leonard D. Shultz, The Jackson Laboratory
NSG-Abo DR4 mice are NOD.scid.Il2Rγcnull ("NSG"; Stock No. 005557) animals also harboring a murine major histocompatibility complex (MHC) class II knock-out allele (Abo) and the DR4β(NT) transgene that encodes a human HLA-DRB1*0401 modified to have improved interaction with murine CD4.
Females that are homozygous for all three mutations and homozygous for the DR4β(NT) transgene, and males that are homozygous for scid, homozygous for Abo, hemizygous for the X-linked Il2Rγcnull mutation and homozygous for the DR4β(NT) transgene, may be collectively referred to as homozygous NSG-Abo DR4 mice.
Although viable and fertile, homozygous NSG-Abo 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.
Homozygous Abo mice do not express MHC class II - they lack cell surface expression of both class II-A and class II-E MHC proteins.
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-Abo DR4 mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG-Abo 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.
Resources for the NSG mouse model, including discussion forum, immunodeficient model comparison, and categorized, up-to-date references.
NSG-Abo DR4 mice are NOD.scid.Il2Rγcnull ("NSG") animals with a murine major histocompatibility complex (MHC) class II knock-out allele (Abo) and the co-injected HLA-DR4-IE transgenes expressing HLA-DRB1*0401 molecules. NSG-Abo DR4 mice harbor several mutations/transgenes, 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 at ~101 Mbp 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 MHC class II knock-out allele (Abo; H2-Ab1tm1Doi) on chromosome 17 was designed by Drs. Diane Mathis and Christophe Benoist (while at INSERM, Strasbourg, France), and is described for Stock No. 010966. NSG animals with the animals with this H2-Ab1 knock-out allele (NSG-Abo) from Stock No. 021885 were used as described below.
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 Eαp 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.
Additionally, some NSG DR4 animals were bred to NSG-Abo mice (Stock No. 021885) - the resulting NSG-Abo DR4 animals are available as Stock No. 031566.
Depending upon the experiment, the following may be appropriate control strain(s):
--NSG-Abo (Stock No. 021885)
--NOD.scid.IL2RγcKO ("NSG"; Stock No. 005557)
--NOD.scid (Stock No. 001303)
--NOD/ShiLtJ inbred mice (Stock No. 001976)
Currently there are no related genes or alleles for this strain.
Females that are homozygous for all three mutations and homozygous for the DR4β(NT) transgene, and males that are homozygous for scid (Prkdcscid), homozygous for Abo (H2-Ab1tm1Doi), hemizygous for the X-linked Il2Rγcnull (Il2rgtm1Wjl) and homozygous for the DR4β(NT) transgene, may be collectively referred to as homozygous NSG-Abo DR4 mice.
When maintaining a live colony, homozygous NSG-Abo DR4 females may be bred with homozygous NSG-Abo DR4 males.
Homozygous NSG-Abo 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-Abo 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.
When using the NSG-Abo DR4 mouse strain in a publication, please cite the originating article(s) and include JAX stock #031566 in your Materials and Methods section.
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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