NOD.Cg-Mcph1^{Tg(HLA-A2.1)1Enge} Prkdc^scid Il2rg^tm1Wjl/SzJ

Stock number: 009617
Product name: NSG-A2
Strain synonyms: NOD scid gamma, HLA-A2.1, A2-NSG, NSG-HLA-A2.1, NSG-A2
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

This strain ships with remnant UID MiniMax microchips implanted subcutaneously in the back. For more information on these RFID chips, including our FAQ, please visit our Mouse Identification page.

NSG-A2 is a humanized mutant strain combining the features of the NOD/ShiLt background, the severe combined immune deficiency mutation (scid), IL2 receptor gamma chain deficiency and expression of human HLA-A2.1 MHC class I molecule. This model may be useful for studying response to human antigens, such as Epstein-Barr virus, possibly representing a unique preclinical model for vaccine development.

Detailed description

The NOD.Cg-Mcph1^{Tg(HLA-A2.1)1Enge} Prkdc^scid Il2rg^tm1Wjl/SzJ mice, commonly known as NOD scid gamma, HLA-A2.1 (NSG-A2, NSG-HLA), express human class I MHC Ag HLA-A2.1 , but do not express the Prkdc gene nor the X-linked Il2rg gene.

The Tg(HLA-A2.1)1Enge transgene integrated into chromosome 8 causing a duplication in Mcph1 (microcephaly, primary autosomal recessive 1). The duplication results in a functional knock-out of Mcph1 in homozygous mice. Founder line 1 has a copy number of 3-8.

Triple mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities (see additional detail in Breeding Considerations / Maintenance section). NSG mice carrying the HLA-A2.1 transgene (homozygous or hemizygous) overcome one of the limitations of immune response seen in the NSG model (Stock No. 005557), in that they develop protective T cell responses against human viral infections, specifically Epstein-Barr virus, exhibiting traits similar to those seen in humans. This model may be useful for studying response to human antigens and represent a unique preclinical model for vaccine development.

Please note that this strain carries the true null interleukin-2 receptor gamma chain mutation and should not be confused with other strains that express a truncated interleukin-2 receptor gamma chain as described in: "Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor gamma chain" Ohbo K. et al. Blood 1996; 87:956-67.

Development

Triple mutant mice were produced by breeding NOD.Cg-Prkdc^scid Tg(HLA-A2.1)1Enge/Sz mice with NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (Stock No. 005557) mice bearing the X-linked Il2rg allele. The Tg(HLA-A2.1)1Enge transgene integrated into chromosome 8 causing a duplication in Mcph1 (microcephaly, primary autosomal recessive 1). Founder line 1 has a copy number of 3-8. The resulting mice were interbred to produce mice homozygous for the Prkdc^scid and Tg(HLA-A2.1)1Enge alleles and homozygous (females) or hemizygous (males) for the X-linked Il2rg^tm1Wjl allele. In 2009, the T1DR received this stock at generation N8F3.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Synonyms: scid
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Marker synonyms: DNAPDcs; DNAPK; DNA-PK; DNAPKc; DNA-PKC; DNA-PKcs; DNPK1; DOXNPH; dxnph; HYRC; HYRC1; IMD26; p350; S473K; slip; XRCC7
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
Synonyms: [KO]gammac; CD132^-; gammac^-; gc^-; Il2rg^tm1Wjll; IL2Rgamma^null
Marker symbol: Il2rg
Marker name: interleukin 2 receptor, gamma chain
Marker synonyms: [g]c; Ab2-183; Cd132; CIDX; common cytokine receptor gamma chain; common gamma chain; gamma C receptor; gamma(c); gammaC; gc; IL-2RG; IMD4; P64; SCIDX; SCIDX1
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.

Allele

Symbol: Mcph1^{Tg(HLA-A2.1)1Enge}
Name: transgene insertion 1, Victor H Engelhard
MGI accession ID: MGI:3056375
Generation method: Transgenic
Attributes: Null/Knockout; Inserted expressed sequence; Humanized sequence
Marker symbol: Mcph1
Marker name: microcephaly, primary autosomal recessive 1
Marker synonyms: 5430437K10Rik; BRIT1; D030046N04Rik; MCT; RGD1560642
Chromosome: 8
Strain of origin: C57BL/6
Expressed genes: HLA-A,major histocompatibility complex, class I, A,human
Molecular note: The transgene contains the full length HLA-A2.1 gene. Expression of human class I MHC Ag HLA-A2.1 was detected on cells from homozygous transgenic spleen, bone marrow, and thymus. Line 1 inserted into the gene at 18736683-18757058 (Build GRCm38/mm10) resulting in a duplication. The duplication results in a functional knock-out. Founder line 1 has a copy number of 3-8.
General note: Expression of this human class I molecule in transgenic mice does not result in expansion of the number of cytotoxic T lymphocyte (CTL) precursors specific for other human class I Ag, HLA-B27 or HLA-A2.2.