• FcRn is a specific receptor for IgG and albumin, composed of MHC class I-related molecules and β2-microglobulin. FcRn binds to IgG and albumin in a pH-dependent manner, maintaining the concentration of IgG and albumin in the plasma and facilitating their transmembrane transport. Cells internalize IgG from the serum through endocytosis. Proteins that do not bind to FcRn are degraded in lysosomes, while IgG bound to FcRn is released back into the bloodstream, thereby extending its half-life.
• A chimeric CDS that encodes full-length human FcRn, followed by rat 3’UTR-STOP is inserted right after rat FcRn ATG to replace the exon 2-4 of rat FcRn gene. The FcRn protein expression will be driven by endogenous rat FcRn promoter, while rat FcRn gene transcription and translation will be disrupted.
• Rat FcRn was only detectable in wild-type SD rats. Human FcRn was exclusively detectable in liver, kidney and spleen of homozygous B-hFcRn rats.
• Application: This product is used for pharmacokinetics, pharmacodynamics and safety evaluation of human immunoglobulin G (IgG) and based on the Fc domain therapeutics.

Gene targeting strategy for B-hFcRn rats. A chimeric CDS that encodes full-length human FcRn, followed by rat 3’UTR-STOP is inserted right after rat FcRn ATG to replace the exon 2-4 of rat FcRn gene. The FcRn protein expression will be driven by endogenous rat FcRn promoter, while rat FcRn gene transcription and translation will be disrupted.

Western blot analysis of FcRn protein expression in homozygous B-hFcRn rats. Various tissue lysates were collected from wild-type SD rats (+/+) and homozygous B-hFcRn rats (H/H), and then analyzed by western blot with species-specific anti-rats FcRn antibody (R&D, AF6775) and anti-human FcRn antibody (Novus Biologicals, NBP1-89128). 40 μg total proteins were loaded for western blotting analysis. Rat FcRn was only detectable in wild-type SD rats. Human FcRn was exclusively detectable in liver, kidney and spleen of homozygous B-hFcRn rats.