The neonatal Fc receptor (FcRn) plays a critical role in IgG recycling and prolonging antibody half-life. Dysregulation of FcRn is linked to autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and myasthenia gravis.

In FcRn humanized mice, the murine Fcgrt gene is replaced by its human counterpart (FCGRT), ensuring that antibodies interact with human FcRn rather than murine FcRn. These mice accurately reflect human antibody pharmacokinetics (PK), enabling more predictive antibody half-life studies, drug efficacy testing, and antibody engineering validation.

Key Advantages

• Complete human gene replacement: Murine Fcgrt replaced by human FCGRT.
• Physiological relevance: Human IgG and albumin recycling faithfully reproduced.
• Drug development utility: Supports antibody half-life optimization and evaluation of FcRn antagonists.
• Normal immune function: No alterations in immune cell subsets or baseline physiology.
• Broad application: Suitable for studies in autoimmune diseases, immunotherapy, and antibody engineering.
• Competitive edge: Provides superior translational predictability compared with FcRn knockout or transgenic models.

Validation

• Human FcRn expression confirmed in homozygous FcRn humanized mice using RT-PCR and Western blot.
• IgG and albumin recycling: Human IgG and albumin show extended half-life in FcRn humanized mice compared with wild-type controls.
• Pharmacokinetics studies: Human therapeutic antibodies exhibit human-like PK profiles in FcRn humanized mice.
• Normal immune profile: Immune cell composition and hematology remain unchanged in FcRn humanized mice.

Applications

• Antibody Pharmacokinetics: Evaluate half-life, clearance, and biodistribution of therapeutic antibodies.
• Fc Engineering Studies: Assess Fc modifications designed to enhance or reduce FcRn binding.
• FcRn Antagonist Testing: Preclinical efficacy evaluation of FcRn-targeted therapies for autoimmune diseases (e.g., myasthenia gravis, pemphigus vulgaris, lupus).
• Albumin-based Therapeutics: Study albumin fusion proteins and FcRn-mediated half-life extension.
• Translational Immunology: Model human FcRn-IgG interactions for clinical predictability.

The human full-length FCGRT cDNA sequence was inserted into exon 2 of the mouse Fcgrt gene.

Strain-specific analysis of FCGRT gene expression was performed in wild-type (WT) and FcRn humanized mice (B-hFcRn) using RT-PCR. Mouse Fcgrt mRNA was detectable in the kidneys of wild-type C57BL/6 (+/+) mice. In contrast, human FCGRT mRNA was exclusively detectable in homozygous FcRn humanized mice (H/H) but not in wild-type controls (+/+).

Strain-specific FcRn protein expression was analyzed in wild-type C57BL/6 (+/+) and homozygous FcRn humanized mice (B-hFcRn, H/H) by western blot using species-specific anti-FcRn antibodies. Mouse FcRn protein was detected in kidney tissue of wild-type mice, whereas human FcRn protein was expressed only in FcRn humanized mice, but not in wild-type controls.

Strain-specific immunoglobulin expression was measured in wild-type C57BL/6JNifdc mice, homozygous FcRn knockout (B-FcRn KO) mice (-/-), and homozygous FcRn humanized mice (B-hFcRn, H/H) using ELISA (SouthernBiotech C57BL/6 Mouse Immunoglobulin Panel, 5300-01B). Serum was collected from female mice (11 weeks old, n=3). The expression levels of mouse immunoglobulins were quantified, and values are expressed as mean ± SEM.

Strain-specific FcRn protein expression patterns were analyzed in homozygous FcRn humanized mice (B-hFcRn, H/H) by western blot. Samples were collected from liver, lung, spleen, small intestine, and kidney. Human FcRn protein expression was detected in all of these tissues, demonstrating physiologically relevant tissue distribution in the humanized FcRn mouse model.

The serum pharmacokinetic (PK) profiles of Ab1 and Ab1-YTE. The effect of the YTE mutation in prolonging antibody half-life was observed only in FcRn humanized mice (B-hFcRn) but not in wild-type controls. Values are expressed as mean ± SEM.

Pharmacokinetic studies were performed using commercial therapeutic antibodies in FcRn humanized mice (B-hFcRn). Serum half-lives in human and monkey were obtained from published research articles. Blood collection was performed continuously, and abrupt PK changes were excluded from the analysis. PK curve fitting was based on the last three blood collection points. Data are shown as mean ± SEM.

A pharmacokinetic (PK) study was performed using Ab-IgG1 and Ab-YTE-IgG1 antibodies in homozygous FcRn humanized mice (B-hFcRn, H/H). Mice were intravenously injected with Ab-IgG1 and Ab-YTE-IgG1 (provided by the client) at time 0. Blood was collected at designated time points, and serum antibody concentrations were measured. The Ab-YTE-IgG1 group (G2) exhibited slower clearance compared with Ab-IgG1 (G1), confirming that the YTE mutation prolongs antibody half-life in the FcRn humanized mouse model. Data provided by the client; values expressed as mean ± SEM.

Q1: What are FcRn humanized mice?

FcRn humanized mice (B-hFcRn) are genetically engineered to replace the murine Fcgrt gene with the human FCGRT gene, enabling expression of human neonatal Fc receptor (FcRn).

Q2: Why are FcRn humanized mice important for antibody drug development?

FcRn regulates IgG and albumin recycling, directly influencing antibody half-life. This model allows accurate preclinical testing of therapeutic antibodies, Fc-engineered variants, and FcRn antagonists.

Q3: Can FcRn humanized mice be used for antibody PK studies?

Yes. FcRn humanized mice reproduce human IgG pharmacokinetics, enabling evaluation of clearance, biodistribution, and half-life extension strategies.

Q4: How do FcRn humanized mice differ from wild-type mice?

Unlike wild-type mice, which recycle IgG via murine FcRn, FcRn humanized mice recycle human IgG and albumin via human FcRn, providing translationally relevant results for clinical antibody studies.

Q5: What diseases can be studied using FcRn humanized mice?

They are particularly valuable for autoimmune diseases involving pathogenic IgG, such as myasthenia gravis, lupus, and pemphigus vulgaris, as well as for metabolic and immunotherapy studies.