Homozygous mice deficient for the ligand-binding alpha chain of Fc gamma RIII lack NK cell-mediated antibody-dependent cytotoxicity and phagocytosis of IgG1-coated particles by macrophages.
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.
FcγRIII- mice are also available backcrossed to C57BL/6 for 13 generations as Stock No. 009637.
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 donating investigator reports that the mice were backcrossed to C57BL/6 for 7 generations (see SNP note below).
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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, at least 2 of 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 mixed C57BL/6J ; 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. The expected coat color from breeding is black.
When using the FcγRIII- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003171 in your Materials and Methods section.