|Strain Name||C57BL/6-Fcgrttm1(FCGRT)/Bcgen||Common Name||B-hFcRn mice|
FCGRT(Fc fragment of IgG receptor and transporter)
FCRN, also known as FCGRT, encodes an Fc receptor which is similar in structure to the MHC class I protein family. Like its prototypic family members, FcRn is a type I membrane protein consisting of a heavy chain containing 3 extracellular immunoglobulin superfamily domains, a single pass transmembrane domain and a short cytoplasmatic tail, and forms an heterodimer with the β2m. FcRn expression has been detected almost ubiquitously in diverse tissues throughout the body including epithelia, endothelia and cells of hematopoietic origin, and it epithelial expression has been shown in the intestines, placenta, kidney and liver. FcRn possesses little diversity and is unable to present Ags, instead, through its capacity to bind IgG and albumin with high affinity at low pH, it regulates the serum half-lives of both of these proteins. In addition, FcRn plays an important role in immunity at mucosal and systemic sites through its ability to affect the lifespan of IgG, as well as its participation in innate and adaptive immune responses. Thus, FcRn might be a good target for drug delivery and disease therapy.
Biocytogen uses gene editing technology to replace FcRn of C57BL/6 mice for the corresponding full-length FcRn of human, developed B-hFcRn humanized mice model. The mice model will facilitate research on therapeutic antibody half-Life evaluation.
Strain specific analysis of FCGRT gene expression in WT and B-hFcRn mice by RT-PCR.
Mouse Fcgrt mRNA was detectable in kidney of wild-type (+/+). Human FCGRT mRNA was detectable only in H/H but not in +/+ mice.
Protein expression analysis
Strain specific analysis of FcRn expression in C57BL/6(+/+) and B-hFcRn mice by western blot.
Kidney was collected from C57BL/6(+/+) mice and homozygous B-hFcRn(H/H) mice and analyzed by western blot with species-specific anti-FcRn antibody. Mouse FcRn was detectable in C57BL/6(+/+) mice. Human FcRn was detectable only in B-hFcRn(H/H) but not in C57BL/6(+/+) mice.
Serum half-life of Ab1 in B-hFcRn mice
PK profiles in B-hFcRn and C57BL/6 mice IV-dosed at 10 mg/kg with Ab1. Data points from mice with high immune response to the injected antibody, demonstrated by mouse antihuman antibody titers of greater than 1 to 1000 and corresponding to abrupt PK changes, were excluded in the analyses.
Different type of IgGs pharmacokinetics in B-hFcRn mice
PK profiles in B-hFcRn and C57BL/6 mice IV-dosed at 10 mg/kg with Ab1(IgG1), Ab2(IgG2) and Ab3(IgG3). Data points from mice with high immune response to the injected antibody, demonstrated by mouse antihuman antibody titers of greater than 1 to 1000 and corresponding to abrupt PK changes, were excluded in the analyses.
The YTE mutation prolongs Abs half-life in B-hFcRn mice