FcRn knock-out mice are unable to recycle IgG or albumin and degrade IgG at an accelerated rate, resulting in low plasma expression levels of both. Further, they are unable to transport IgG across epithelial barriers (e.g., neonatal gut and placenta), allowing for the study of maternal passive immunity. This model may be useful in testing therapeutic compounds and their involvement in the FcRn pathway, or as a control for humanized FcRn transgenics.Read More +
The neonatal Fc receptor (FcRn), encoded by the Fcgrt gene, is a MHC class I like molecule. One of its functions is to protect IgG and albumin from degradation, and to mediate the transport of IgG across epithelial cells. Further, it is plays a role in antigen presentation by professional antigen presenting cells. It has been demonstrated that FcRn is critical for the materno-fetal transport and intestinal uptake of IgG.
Homozygous FcRn α-chain knockout mice are viable and fertile. No gene product (mRNA or protein) is detected by quantitative PCR analysis of liver cDNA or Western blot analysis of small intestine from homozygotes. Homozygotes exhibit plasma albumin concentration approximately 45% of levels observed in wild-type controls, reduced IgG levels, as well as diminished perinatal maternal IgG transport. FcRn -/- mice are resistant to experimentally induced, serum-transfer autoimmune arthritis, as well as experimentally induced bullous pemphigoid, pemphigus foliaceus, and pemphigus vulgaris. Homozygotes are more sensitive to experimentally induced Lyme's disease arthritis, with more severe ankle swelling, joint involvement and decreased anti Borrelia burgdorferi antibody serum levels. IgG accumulates in the glomerular basement membranes of aging mutants, and clearance of IgG from the kidneys is impaired. This strain may be useful in studies of IgG-mediated autoimmune diseases, IgG homeostasis, IgG-mediated phagocytosis and maternal passive immunity and serves as a control for humanized FcRn transgenics (see Stock Numbers: 004919 and 014565)
A targeting vector was designed to replace 1588 nucleotide fragments (encoding promoter sequence 5' of the transcriptional start site, exon 1, intron 2, and most of exon 2) with a PGK-Neor cassette. The vector was electroporated into 129X1/SvJ-derived ESV/J-1182 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. The mice were then backcrossed to C57BL/6J for 11 generations.
|Allele Name||targeted mutation 1, Derry C Roopenian|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Fcgrt, Fc receptor, IgG, alpha chain transporter|
|Strain of Origin||129X1/SvJ|
|Molecular Note||Sequence from exon 1 and part of exon2 was replaced with a PGK-neo cassette. Quantitative PCR of liver cDNA indicated the absence of mRNA. Western blot analysis of neonatal intestinal extracts failed to reveal protein product.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the FcRn- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003982 in your Materials and Methods section.
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