NOD.Cg-Ggta1^tm1Jbl Prkdc^scid Il2rg^tm1Wjl/J

Stock number: 039051
Product name: Hu-NSG/α-Gal^null
Strain synonyms: NSG GT-KO
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

These Hu-NSG/α-Gal^null mice have a neo cassette inserted into the catalytic domain in exon 9 of the alpha 1, 3 galactosyltransferase (Ggta1) gene, resulting in inactivation of this enzyme. On the NSG genetic background, these mice mimic humans in that they do not synthesize α-gal epitopes and secrete human anti-Gal Abs, but no murine anti-Gal Abs. These mice may be useful for preclinical evaluations of viral and tumor vaccines based on a-Gal epitopes, human-specific immune responses, xenotransplantation studies, and in vivo biomaterials evaluation.

Detailed description

Anti-Gal (anti-alpha-Gal) is the most abundant natural antibody in humans, it constitutes ∼1% of serum immunoglobulins in all young and elderly individuals that are not severely immunocompromised. Anti-Gal Ab is continuously produced throughout life as an immunological response to antigenic stimulation by bacteria of the normal flora. Anti-Gal Ab interacts specifically with a carbohydrate antigen called the ‘α-gal epitope’ (Galα1-3GalΒ1-4GlcNAc-R) on glycolipids and glycoproteins. Anti-Gal can contribute to several immunological pathogeneses, for example, anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Expression of the α-gal epitope may also result in autoimmune processes, as in Graves' disease and "autoimmune like" inflammatory reactions seen in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. However, anti-Gal may also be exploited for various clinical uses such as increasing the immunogenicity of microbial vaccines, targeting tumor cells for uptake by antigen-presenting cells and scarless regeneration of skin and myocardial injuries by alpha-gal nanoparticles.

These Hu-NSG/α-Gal^null mice have a neo cassette inserted into the catalytic domain in exon 9 of the alpha 1, 3 galactosyltransferase (Ggta1) gene, resulting in inactivation of this enzyme. On the NSG genetic background, these mice mimic humans in that they do not synthesize α-gal epitopes and secrete human anti-Gal Abs, but no murine anti-Gal Abs. These mice may be useful for preclinical evaluations of viral and tumor vaccines based on a-Gal epitopes, human-specific immune responses, xenotransplantation studies, and in vivo biomaterials evaluation.

This Gal KO mutation is also available on a mixed genetic background as Stock No. 038382.

As of October 2025, it is the experience of The Jackson Laboratory that females that are homozygous for all three mutations and males that are homozygous for Prkdc^scid and Ggta1^tm1Jbl and hemizygous for Il2rg^tm1Wjl may develop cataracts.

Maintaining these severely immunocompromised mice under specific pathogen-free conditions is recommended to promote their overall health. Please see our NSG housing and breeding information for additional details.

Development

A targeting vector was designed to insert a neomycin resistance (neo) cassette into the catalytic domain in exon 9 of the alpha 1, 3 galactosyltransferase (Ggta1) gene, resulting in inactivation of the enzyme. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to F1(C57BL/6J × DBA/2J) females. These mice Gal KO or GT-KO mice were sent to The Jackson Laboratory on a mixed genetic background as Stock No. 038382. Some of these mice where further backcrossed to NSG mice (Stock No. 005557) to create this new strain, Stock No. 039051.

Allele

Symbol: Ggta1^tm1Jbl
Name: targeted mutation 1, John B Lowe
MGI accession ID: MGI:1857435
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: alpha1,3GT-; alpha1,3GT KO; Gal KO; GalT^-; Gt⁰
Marker symbol: Ggta1
Marker name: glycoprotein galactosyltransferase alpha 1, 3
Marker synonyms: a1/3GTP; alpha Gal; alpha3GalT; Gal; GALT; Ggta; Ggta-1; GGTA1P; glycoprotein alpha galactosyl transferase 1; GLYT2
Chromosome: 2
Strain of origin: 129S2/SvPas
Molecular note: A PGK-neomycin resistance cassette was inserted into the catalytic domain in exon 9 of the Ggta1 gene. The disruption deleted 500 bp of coding sequence. Immunohistochemical studies did not detect terminal alpha galactosides in tissues of homozygous mutant mice.

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.