STOCK Ggta1^tm1Jbl/NbndrJ

Stock number: 038382
Product name: GT-KO
Strain synonyms: Gal KO
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Sensorineural Research

Description

These Gal KO or GT-KO 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. These mice do not synthesize α-gal epitopes and they can produce anti-Gal Abs with characteristics similar to those of human natural anti-Gal Abs. These mice may be useful for studying anti-Gal immune responses, xenotransplantation studies, amplification of tumor and viral vaccine efficacy, and alpha-gal therapies for regeneration of injured tissues.

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 Gal KO or GT-KO 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. These mice do not express α-gal. In contrast to all wildtype mice, Gal KO mice are not immunotolerant to α-gal epitopes and can produce anti-Gal Abs with characteristics similar to those of human anti-Gal Abs. The healing time of excisional skin wounds treated with α-gal nanoparticles in these mice is twice as fast and scar formation is much lower than in physiologic healing or in wildtype mice. Also, these mice get cataracts with an onset around 12 weeks of age.

Since this strain is maintained on a mixed genetic background containing C57BL/6J and DBA/2J, the MHC haplotype can be either H2^b/b, H2^b/d, or H2^d/d.

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 maintained on a mixed genetic background. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL6/J oocytes (Stock No. 000664).

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.