NOD.Cg-B2m^tm1Unc Prkdc^scid H2^dlAb1-Ea Il2rg^tm1Wjl/SzJ

Stock number: 030547
Product name: NSG-B2M^null(IA IE)^null
Strain synonyms: NSG-B2M^null (IA IE)^null
Research areas: Cancer Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Research Tools, Virology Research

Description

NSG-B2m^null (IA IE)^null quadruple mutant mice combine the features of the severe combined immune deficiency mutation (scid), IL2 receptor gamma chain deficiency, MHC class I molecule (beta-2 microglobulin) deficiency, and MHC class II molecule deficiency (IA IE) and exhibit a resistance to graft versus host disease (GVHD). Rapid clearance of human IgG is observed in this strain. They provide a model useful to study human immunity in the absence of GVHD and to evaluate antibody-based therapeutics.

Detailed description

NSG-B2m^null (IA IE)^null quadruple mutant mice combine the features of the severe combined immune deficiency mutation or scid (B and T cell deficiency), IL2 receptor gamma chain deficiency (NK cell deficiency), MHC class I molecule (beta-2 microglobulin) deficiency, and MHC class II molecule deficiency (IA IE). Quadruple mutant mice are viable, normal in size and do not display any gross physical or behavioral abnormalities. The survival of non-irradiated mice injected with 10 x 10⁶ human peripheral blood mononuclear cells (PBMC) is greater than 100 days, with 15/18 of the mice exhibiting no symptoms of GVHD for up to 125 days. This model may be useful to study human immunity in the absence of GVHD and to evaluate antibody-based therapeutics.

The serum half-life of human IgG is greatly reduced in B2m mutant strains due to defective FcRn function (Junghans and Anderson, 1996, Praetor and Hunziker, 2002).

Development

This strain was generated in two steps. First, the H2^dlAb1-Ea allele from B6.129S7-H2^dlAb1-Ea/J (Stock No. 003584) was crossed to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/J (Stock No. 005557) for a minimum of five generations. Second, mice from this cross and mice from NOD.Cg-B2m^tm1Unc Prkdc^scid Il2rg^tm1Wjl/SzJ (Stock No. 010636) were interbred. Progeny were intercrossed to generate females that are homozygous for the B2M KO, scid, MHC II (IA-IE) KO and Il2rg KO alleles. Males are homozygous for the B2M KO, scid, and MHC II (IA IE) KO alleles and hemizygous for the X-linked Il2rg KO allele.

Allele

Symbol: B2m^tm1Unc
Name: targeted mutation 1, University of North Carolina
MGI accession ID: MGI:1857133
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: b2m^null; beta2M-; beta2m⁰; beta2m^null; beta2m^o; beta2m^tm1Unc; beta2MKO; beta2-m-KO; I⁰; MHC-I^-
Marker symbol: B2m
Marker name: beta-2 microglobulin
Marker synonyms: AMYLD6; beta 2 microglobulin; beta2-m; IMD43; Ly-m11; MHC1D4
Chromosome: 2
Strain of origin: 129P2/OlaHsd
Molecular note: Insertion of a neomycin-resistance gene into the second exon.

Allele

Symbol: H2^dlAb1-Ea
Name: targeted deletion, H2 complex
MGI accession ID: MGI:2658725
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: (IA IE)^null; ABeta^o; II^delta; MHC class II^delta; MHC II KO; MHC II^-; MHC II⁰; MHC II^delta; MHCII^-; MHCII^delta; MHC-II^delta
Marker symbol: H2
Marker name: histocompatibility-2, MHC
Marker synonyms: H-2; MHC-II
Chromosome: 17
Strain of origin: 129S2/SvPas
Molecular note: A 78.8 kb deletion disrupting Class II MHC genes was induced in 129S2/SvPas-derived H1 embryonic stem (ES) cells via Cre recombination. A hygro-resistance cassette was inserted at the deletion site. The deletion spans from the second exon of the H2-Ab1 gene the third exon of the H2-Ea gene. The H2-Aa, H2-Eb1 and H2-Eb2 genes are completely deleted.

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.