Mice homozygous for the Fcgr3tm1Sjv (Fc receptor, IgG, low affinity III) targeted mutation lack NK cell-mediated antibody-dependent cytotoxicity, phagocytosis of IgG1-coated particles by macrophages, IgG-mediated mast cell degranulation, are resistant to IgG-dependent passive cutaneous anaphylaxis, and exhibit an impaired Arthus reaction. This mutant mouse strain may be useful in studies of allergic response, anaphylaxis, and hypersensitive immune response.
Dr. J. S. Verbeek, Leiden University Medical Center
Mice homozygous for the Fcgr3tm1Sjv targeted mutation, which eliminates the ligand-binding alpha chain of FcgammaRIII, are viable and fertile. Homozygous mutant mice lack NK cell-mediated antibody-dependent cytotoxicity, phagocytosis of IgG1-coated particles by macrophages, and IgG-mediated mast cell degranulation. They are resistant to IgG-dependent passive cutaneous anaphylaxis, and exhibit an impaired Arthus reaction. SNP analysis completed by the Donating Investigator shows that these mice carry the C57BL/6 derived Sle1b, systematic lupus erythematosus susceptibility 1b, locus.
A targeting vector containing a PGK-hygromycin resistance cassette was used to disrupt exon 4 and the 5' end of exon 5, which encode the ligand-binding EC2 domain and part of the transmembrane region, respectively. The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem cells, the targeted ES clones injected into C57BL/6 blastocysts, and the resulting chimeras bred to C57BL/6 females. The mice were then backcrossed to C57BL/6JIco for 13 generations (see SNP notes below) and designated line 2. SNP analysis completed by the Donating Investigator shows that these mice carry the C57BL/6 derived Sle1b, systematic lupus erythematosus susceptibility 1b, locus. Upon arrival at The Jackson Laboratory the mice were crossed to C57BL/6J once to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1, J Sjef Verbeek|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||FcgammaRIII-; Fcgr3tm1Sjv|
|Gene Symbol and Name||Fcgr3, Fc receptor, IgG, low affinity III|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A hygromycin selection cassette replaced a genomic fragment containing sequences encoding the ligand binding and part of the transmembrane domains. RT-PCR analysis on NK fractions of splenocytes derived from homozygous mice demonstrated that no detectable transcript was produced from this allele. Flow cytometry analysis on NK cells, B lymphocytes, macrophages and neutrophils confirmed that no detectable cell surface protein was encoded by this allele.|
|Mutations Made By|| |
Dr. J. Verbeek, Leiden University Medical Center
When maintaining a live colony, these mice can be bred as homozygotes.
When using the FcγRIII- mouse strain in a publication, please cite the originating article(s) and include JAX stock #009637 in your Materials and Methods section.