Basic Information
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Targeting strategy
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Gene targeting strategy for B-hFcRn mice. The human full-length FCGRT cDNA sequence was inserted in the Fcgrt exon2 of wild-type mice.
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mRNA expression analysis
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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.
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Protein expression analysis
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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.
Strain specific analysis of FcRn expression pattern in B-hFcRn mice by western blot. Liver, lung, spleen, small intestine, and kidney was collected from homozygous B-hFcRn (H/H) mice and analyzed by western blot with species-specific anti-FcRn antibody. The above organizations have detected the expression of the FcRn protein in homozygous B-hFcRn mice.
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The expression results of immunoglobulins in serum
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Strain specific immunoglobulins expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hFcRn mice by ELISA. Serum was collected from wild-type C57BL/6N mice (+/+), homozygous B-FcRn KO mice (-/-) and homozygous B-hFcRn mice (H/H) (female, 11-week-old, n=3). Expression level of mouse immunoglobulins were analyzed by ELISA (SouthernBiotech C57BL/6 Mouse Immunoglobulin Panel, 5300-01B). Values are expressed as mean ± SEM.
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The YTE mutation prolongs Abs half-life in B-hFcRn mice
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The serum pharmacokinetics profiles for Ab1 and Ab1-YTE are shown. The effect of YTE in prolonging the half-life of antibodies is only observed in B-hFcRn mice but not in wild-type mice.
PK study of Ab-IgG1 and Ab-YTE-IgG1 in homozygous B-hFcRn mice. Homozygous B-hFcRn mice were intravenously injected with Ab-IgG1 (Provided by the client) and Ab-YTE-IgG1 (Provided by the client) at time 0. Blood was collected at specified timepoints and serum was analyzed for Ab concentrations. The G2 exhibited slower clearance of Ab compared to the G1, indicating the effect of YTE in prolonging the half-life of antibodies is observed in B-hFcRn mice. (The data comes from the client). Values are expressed as mean ± SEM.
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Serum half-life of commercial antibody drug in B-hFcRn mice
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- The test drugs are commercial drugs
- The half-life in humans and monkeys of test drugs from research articles
- Blood collection: Continuous
- Abrupt PK changes were excluded in the analyses
- Curve fitting: The last three blood collection points
- Data are shown in mean ± SEM
