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. 2018 Oct 15;8(4):115.
doi: 10.3390/biom8040115.

FcRn Expression in Wildtype Mice, Transgenic Mice, and in Human Tissues

Tommy Li  1 , Joseph P Balthasar  2
Affiliations

FcRn Expression in Wildtype Mice, Transgenic Mice, and in Human Tissues

Tommy Li et al. Biomolecules. .

Abstract

Quantitative real-time PCR and Western blot methods were developed to assess neonatal Fc-receptor (FcRn) mRNA and protein expression in human FcRn transgenic mice, Swiss Webster mice, and in select human tissues. Additionally, FcRn turnover was evaluated via pulse-chase. FcRn mRNA expression was significantly higher in transgenic mice when compared to mouse FcRn mRNA in Swiss Webster mice and it ranged from 184-fold higher in the kidney to 109,000-fold higher in the skin. FcRn protein expression was found to be 13-fold lower in kidney to 5.6-fold higher in lung obtained from transgenic mice compared to FcRn protein expression in lung samples obtained from Swiss Webster mice. FcRn protein expression in human liver and small intestine tissues matched more closely with FcRn expression in Swiss Webster mice but were significantly lower when compared to values found from Swiss Webster and transgenic mice. Although FcRn mRNA expression correlated significantly with protein expression (p < 0.0005), the correlation coefficient was only 0.113. As such, the measurement of FcRn protein may be preferred to FcRn mRNA for quantitative applications. Significant differences were found in FcRn expression in transgenic mice, Swiss Webster mice, and human tissues, which may have implications for the use of mouse models in the assessment of monoclonal antibody disposition, efficacy, and safety.

Keywords: FcRn; human FcRn transgenic mouse; mRNA; protein; tissue expression.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The comparison of FcRn mRNA expression among Swiss Webster mice, transgenic mice, and select human tissues. Data are expressed in terms of copy numbers per μg of extracted RNA. Data are mean ± standard deviation (SD) from 5 Swiss Webster mice, 3 transgenic mice, liver samples from 3 adult human subjects, and small intestine samples from 3 adult human subjects.
Figure 2
Figure 2
Identification of the human neonatal Fc receptor (hFcRn) band in transgenic mouse tissues. Various hFcRn transgenic mouse tissues probed with anti-hFcRn antibody (A) or 7E9 (B). Lane 1 is a molecular weight marker. Lane 2 is a recombinant hFcRn spiked into wild type mouse liver tissue extract. Lane 3–7 are human FcRn transgenic mouse muscle, lung, kidney, heart, and gastrointestinal (GI) tissue extract. Calculated molecular weight of each band is displayed below the corresponding band.
Figure 3
Figure 3
Comparison of tissue FcRn protein expression among Swiss Webster mice, transgenic mice, and humans. The data are expressed in tissue average FcRn concentration. Data are mean ± SD from 5 Swiss Webster mice, 3 transgenic mice, liver samples from 3 adult human subjects, and GI samples from 3 adult human subjects.
Figure 4
Figure 4
Comparison of tissue mFcRn mRNA and protein expression pattern in Swiss Webster mice (A) and comparison of tissue hFcRn mRNA and protein expression pattern in transgenic mice. (B) Data are mean ± SD from 5 Swiss Webster mice and 3 transgenic mice.
Figure 5
Figure 5
Correlation between mFcRn mRNA and protein expression in Swiss Webster mice (A) and transgenic mice (B). Individual mouse tissue mRNA abundance plotted against tissue protein abundance. Regression analysis showed significant (p < 0.0005) correlation between tissue FcRn mRNA and protein expression in Swiss Webster mice with R2 value of 0.1131. Regression analysis showed no significant correlation between tissue FcRn mRNA and protein expression in transgenic mice.
Figure 6
Figure 6
Degradation of 35S-methionine labeled FcRn in EA.hy926 cells. Decline in 35S-methionine labeled FcRn with time is expressed as a percent of labeled FcRn at 0 h. Each data point represents cells collected from a single T-flask. The fitting of a bi-exponential model to the data is shown by a solid line.
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