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

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 sig...

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Autores principales: Li, Tommy, Balthasar, Joseph P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316262/
https://www.ncbi.nlm.nih.gov/pubmed/30326650
http://dx.doi.org/10.3390/biom8040115
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author Li, Tommy
Balthasar, Joseph P.
author_facet Li, Tommy
Balthasar, Joseph P.
author_sort Li, Tommy
collection PubMed
description 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.
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spelling pubmed-63162622019-01-10 FcRn Expression in Wildtype Mice, Transgenic Mice, and in Human Tissues Li, Tommy Balthasar, Joseph P. Biomolecules Article 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. MDPI 2018-10-15 /pmc/articles/PMC6316262/ /pubmed/30326650 http://dx.doi.org/10.3390/biom8040115 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Tommy
Balthasar, Joseph P.
FcRn Expression in Wildtype Mice, Transgenic Mice, and in Human Tissues
title FcRn Expression in Wildtype Mice, Transgenic Mice, and in Human Tissues
title_full FcRn Expression in Wildtype Mice, Transgenic Mice, and in Human Tissues
title_fullStr FcRn Expression in Wildtype Mice, Transgenic Mice, and in Human Tissues
title_full_unstemmed FcRn Expression in Wildtype Mice, Transgenic Mice, and in Human Tissues
title_short FcRn Expression in Wildtype Mice, Transgenic Mice, and in Human Tissues
title_sort fcrn expression in wildtype mice, transgenic mice, and in human tissues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316262/
https://www.ncbi.nlm.nih.gov/pubmed/30326650
http://dx.doi.org/10.3390/biom8040115
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