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

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
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.

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
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.