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Sex difference in EGFR pathways in mouse kidney-potential impact on the immune system

BACKGROUND: Epidermal growth factor receptor (Egfr) has been the target of several drugs for cancers. The potential gender differences in genes in the Egfr axis have been suggested in humans and in animal models. Female and male mice from the same recombinant inbred (RI) strain have the same genomic...

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Autores principales: Liu, Fengxia, Jiao, Yan, Jiao, Yun, Garcia-Godoy, Franklin, Gu, Weikuan, Liu, Qingyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122204/
https://www.ncbi.nlm.nih.gov/pubmed/27881077
http://dx.doi.org/10.1186/s12863-016-0449-3
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author Liu, Fengxia
Jiao, Yan
Jiao, Yun
Garcia-Godoy, Franklin
Gu, Weikuan
Liu, Qingyi
author_facet Liu, Fengxia
Jiao, Yan
Jiao, Yun
Garcia-Godoy, Franklin
Gu, Weikuan
Liu, Qingyi
author_sort Liu, Fengxia
collection PubMed
description BACKGROUND: Epidermal growth factor receptor (Egfr) has been the target of several drugs for cancers. The potential gender differences in genes in the Egfr axis have been suggested in humans and in animal models. Female and male mice from the same recombinant inbred (RI) strain have the same genomic components except the sex difference. A population of different RI mouse strains allows to conduct precise analysis of molecular pathways and regulation of Egfr between female and male mice. METHODS: The whole genome expression profiles of 70 genetically diverse RI strains of mice were used to compare three major molecular aspects of Egfr gene: the relative expression levels, gene network and expression quantitative trait loci (eQTL) that regulate the expression of Egfr between female and male mice. RESULTS: Our data showed that there is a significant sex difference in the expression levels in kidney. A considerable number of genes in the gene network of Egfr are sex differentially expressed. The expression levels of Egfr in mice are statistical significant different between C57BL/6 J (B6) and DBA/2 J (D2) genotypes in male while no difference in female mice. The eQTLs that regulate the expression levels of Egfr between female and male mice are also different. Furthermore, the differential expression levels of Egfr showed significantly different correlations with two known biological traits between male and female mice. CONCLUSION: Overall there is a substantial sex difference in the Egfr pathways in mice. These data may have significant impact on drug target design, development, formulation, and dosage determinant for women and men in clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-016-0449-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-51222042016-11-30 Sex difference in EGFR pathways in mouse kidney-potential impact on the immune system Liu, Fengxia Jiao, Yan Jiao, Yun Garcia-Godoy, Franklin Gu, Weikuan Liu, Qingyi BMC Genet Research Article BACKGROUND: Epidermal growth factor receptor (Egfr) has been the target of several drugs for cancers. The potential gender differences in genes in the Egfr axis have been suggested in humans and in animal models. Female and male mice from the same recombinant inbred (RI) strain have the same genomic components except the sex difference. A population of different RI mouse strains allows to conduct precise analysis of molecular pathways and regulation of Egfr between female and male mice. METHODS: The whole genome expression profiles of 70 genetically diverse RI strains of mice were used to compare three major molecular aspects of Egfr gene: the relative expression levels, gene network and expression quantitative trait loci (eQTL) that regulate the expression of Egfr between female and male mice. RESULTS: Our data showed that there is a significant sex difference in the expression levels in kidney. A considerable number of genes in the gene network of Egfr are sex differentially expressed. The expression levels of Egfr in mice are statistical significant different between C57BL/6 J (B6) and DBA/2 J (D2) genotypes in male while no difference in female mice. The eQTLs that regulate the expression levels of Egfr between female and male mice are also different. Furthermore, the differential expression levels of Egfr showed significantly different correlations with two known biological traits between male and female mice. CONCLUSION: Overall there is a substantial sex difference in the Egfr pathways in mice. These data may have significant impact on drug target design, development, formulation, and dosage determinant for women and men in clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-016-0449-3) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-24 /pmc/articles/PMC5122204/ /pubmed/27881077 http://dx.doi.org/10.1186/s12863-016-0449-3 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Liu, Fengxia
Jiao, Yan
Jiao, Yun
Garcia-Godoy, Franklin
Gu, Weikuan
Liu, Qingyi
Sex difference in EGFR pathways in mouse kidney-potential impact on the immune system
title Sex difference in EGFR pathways in mouse kidney-potential impact on the immune system
title_full Sex difference in EGFR pathways in mouse kidney-potential impact on the immune system
title_fullStr Sex difference in EGFR pathways in mouse kidney-potential impact on the immune system
title_full_unstemmed Sex difference in EGFR pathways in mouse kidney-potential impact on the immune system
title_short Sex difference in EGFR pathways in mouse kidney-potential impact on the immune system
title_sort sex difference in egfr pathways in mouse kidney-potential impact on the immune system
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122204/
https://www.ncbi.nlm.nih.gov/pubmed/27881077
http://dx.doi.org/10.1186/s12863-016-0449-3
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