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Updated: Mar 11, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Sex difference in EGFR pathways in mouse kidney-potential impact on the immune system
Fengxia Liu1,2, Yan Jiao2, Yun Jiao3
1The Fourth Hospital, Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
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.
Insights
Significant sex differences exist in the epidermal growth factor receptor (Egfr) pathway in mice. These findings highlight potential impacts on cancer drug development and clinical trial design for men and women.
Area of Science:
- Genomics
- Molecular Biology
- Pharmacology
Background:
- Epidermal growth factor receptor (Egfr) is a key target in cancer therapy.
- Potential sex-based genetic differences in the Egfr pathway are suggested in humans and animal models.
- Recombinant inbred (RI) mouse strains offer a model to precisely analyze sex differences in Egfr regulation.
Purpose of the Study:
- To compare sex differences in Egfr gene expression levels, network, and regulatory quantitative trait loci (eQTLs) across genetically diverse mouse strains.
- To investigate sex-specific regulation of Egfr.
- To identify potential sex-based variations in Egfr pathway activity.
Main Methods:
- Whole genome expression profiling of 70 genetically diverse RI mouse strains.
- Comparative analysis of Egfr expression levels, gene networks, and eQTLs between male and female mice.
- Statistical analysis to determine significant sex differences and genotype effects.
Main Results:
- Significant sex differences in Egfr expression were observed in the kidney.
- Numerous genes within the Egfr network exhibited sex-differential expression.
- Egfr expression differed significantly between C57BL/6J and DBA/2J genotypes in males, but not in females.
- Sex-specific eQTLs regulating Egfr expression were identified.
- Differential Egfr expression showed varied correlations with biological traits between sexes.
Conclusions:
- Substantial sex differences exist in mouse Egfr pathways.
- These findings have implications for sex-specific drug target design, development, and clinical trial considerations.
- Understanding sex-based variations in Egfr is crucial for personalized medicine.
