NOD.Cg-Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz Prkdc^scid Il2rg^tm1Wjl/GckRolyJ

Stock number: 012479
Product name: NSG-DR1
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

These mutant mice combine the features of the NOD/ShiLtJ background, the severe combined immune deficiency mutation (scid), IL2 receptor gamma chain deficiency and a human/mouse chimeric MHC Class II transgene (Tg(HLA-DRB1*01)1Dmz). This mutant mouse strain may be useful for xenotransplantation and vaccine development.

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Detailed description

Mice that are homozygous for the targeted transgene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These mutant mice combine the features of the NOD/ShiLtJ background, the severe combined immune deficiency mutation (scid), IL2 receptor gamma chain deficiency and a human/mouse chimeric MHC Class II transgene (Tg(HLA-DRB1*01)1Dmz). This mutant mouse strain is expected to be useful for xenotransplantation and vaccine development.

Development

A transgenic construct containing the mouse MHC Class II H2-Ea and H2-Eb1 genes engineered to encode proteins in which the alpha1 domain (amino acids 1-85) and the beta1 domain (amino acids 1-96) were replaced by the corresponding amino acids of the human MHC Class II protein encoded by HLA-DRA1*0101 and HLA-DRB1*0101. Mice were generated by injecting the construct into fertilized (C57BL/6XSJL/J)F2 oocytes. Founder mice were backcrossed for three generations to B10.M-H-2^f and then intercrossed to fix the H-2^f locus. Mice were backcrossed to NOD.CB17-Prkdc^scid mice for 8 generations and then crossed to NOD.Cg-Prkdc^scidIl2rg^tm1Wjl (NSG); the donating investigator did not select for the H-2^f haplotype while backcrossing. Progeny were intercrossed and selected for both targeted mutations and the transgene. Upon arrival, mice were bred to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/J (Stock No. 005557) for at least 1 generation to establish the colony.

Allele

Symbol: Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz
Name: transgene insertion 1, Dennis M Zaller
MGI accession ID: MGI:3809457
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz
Marker name: transgene insertion 1, Dennis M Zaller
Chromosome: 5
Strain of origin: (C57BL/6 x SJL/J)F2
Expressed genes: HLA-DRA,major histocompatibility complex, class II, DR alpha,human; HLA-DRB1,major histocompatibility complex, class II, DR beta 1,human
Site of expression: virtually all cells in peripheral blood that express MHC Class II

Molecular note: A chimeric MHC class II complex was created by fusing the human peptide binding domains of class II alpha and beta chains to the CD4 binding domains of murine class II alpha or beta chains. The was done by the construction of two separate transgene constructs. The alpha1 and beta1 domains isolated from human DRA1*0101 and DRB1*0101 replaced the corresponding alpha1 and beta1 domains of the H2-Ea and H2-Eb1 genes that make up mouse I-E^d. The native murine promoters were left intact. These transgene constructs were co-injected into fertilized oocytes and the founder mice with the highest expression of the chimeric MHC was chosen for further propagation. Flow cytometry analysis indicates that virtually all cells in peripheral blood that express endogenous MHC-II also express the chimeric MHC-II. The transgene construct was later shown (in J:126700) to have inserted into chromosome 5.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Chromosome: 16
Strain of origin: C.BKa-Igh^b/Icr
Site of expression: T and B lymphocytes.
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

Symbol: Il2rg^tm1Wjl
Name: targeted mutation 1, Warren J Leonard
MGI accession ID: MGI:1857455
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Il2rg
Marker name: interleukin 2 receptor, gamma chain
Chromosome: X
Strain of origin: 129S4/SvJae
Site of expression: Primarily lymphoid cells.
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.