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David A Sullivan, Raheleh Rahimi Darabad, Shaohui Liu, Wendy R Kam; Are Mice Relevant Models for Understanding Sex-Related Differences in the Human Meibomian Gland?. Invest. Ophthalmol. Vis. Sci. 2014;55(13):16.
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One of the most striking features of dry eye disease (DED) is that it occurs predominantly in women. We hypothesize that this female prevalence is linked to sex-related differences that exist in the anatomy, molecular biology and physiology of the meibomian gland (MG). This gland plays a critical role in maintaining the tear film, and its dysfunction (MGD) is believed to be the major cause of DED. To better understand the factors that underlie MG sexual dichotomy and promote DED in women, we seek to identify an optimal model for the human MG. Our goal in this study was to determine whether a murine MG is such a model. Towards that end, we examined whether sex differences in MG gene expression are the same in mice and humans.
After obtaining IRB or IACUC approval, eyelid tissues (n = 5 to 36 eyelids and 3 to 7 samples per sex/species) were collected from age-matched humans and BALB/c mice. MGs were isolated and processed for RNA extraction and the evaluation of gene expression by using Illumina BeadChips and Geospiza bioinformatics.
Our analysis of the 500 most highly expressed genes from human (10,099 genes) and mouse (18,302 genes) MGs showed that only 23.4% were the same. If ribosomal genes were excluded, only 16.6% of the genes were similar. Our comparison of the 100 genes with the greatest sex-associated differences in human (e.g. lysozyme, 18.2-fold, M>F) and mouse (e.g. androgen binding protein zeta, 109-fold, F>M) MGs demonstrated that none were the same. Sex significantly influenced the gene expression of a number of chromosomes, but the nature of this activity was species-specific. Further, sex exerted a significant impact on numerous biological process, molecular function and cellular component ontologies, as well as many KEGG pathways, but these effects were also primarily species-specific.
Our results demonstrate that mice are not appropriate models for understanding sex-related differences in gene expression of the human MG. (Supported by NIH grant EY05612 and the Margaret S. Sinon Scholar in Ocular Surface Research fund)
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