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. 2016 Jul;8(5):848-53.
doi: 10.1080/19420862.2016.1178436. Epub 2016 Apr 22.

Tissue expression profile of human neonatal Fc receptor (FcRn) in Tg32 transgenic mice

Yao-Yun Fan  1 , Lindsay B Avery  1 , Mengmeng Wang  1 , Denise M O'Hara  1 , Sheldon Leung  1 , Hendrik Neubert  1
Affiliations

Tissue expression profile of human neonatal Fc receptor (FcRn) in Tg32 transgenic mice

Yao-Yun Fan et al. MAbs. 2016 Jul.

Abstract

The neonatal Fc receptor (FcRn) is a homeostatic receptor responsible for prolonging immunoglobulin G (IgG) half-life by protecting it from lysosomal degradation and recycling it to systemic circulation. Tissue-specific FcRn expression is a critical parameter in physiologically-based pharmacokinetic (PBPK) modeling for translational pharmacokinetics of Fc-containing biotherapeutics. Using online peptide immuno-affinity chromatography coupled with high resolution mass spectrometry, we established a quantitative FcRn tissue protein expression profile in human FcRn (hFcRn) transgenic mice, Tg32 homozygous and hemizygous strains. The concentration of hFcRn across 14 tissues ranged from 3.5 to 111.2 pmole per gram of tissue. Our hFcRn quantification data from Tg32 mice will enable a more refined PBPK model to improve the accuracy of human PK predictions for Fc-containing biotherapeutics.

Keywords: Antibody; IA-LC-HRMS; PBPK models; Tg32; human FcRn; tissue-based target quantification; transgenic mice.

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Figures

Figure 1.
Figure 1.
Tissue extraction reproducibility and heterogeneity from independent lysate preparation of dissected tissue pieces resulting from the same lung, muscle, small and large intestine samples from both homozygous and hemizygous mice showing (A) protein concentration and (B) hFcRn expression. Protein concentration was determined by absorbance at 280 nm.
Figure 2.
Figure 2.
Human FcRn tissue expression profile in (A) Tg32- homozygous and (B) Tg32-hemizygous mice.
See this image and copyright information in PMC

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