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Xiang Shen, Ilham Putra, Neda Afsharkhamseh, Anas Kachlan, Medi Eslani, Ali R Djalilian; Sex differences in the corneal disease in Notch1 conditional knockout mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2607.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously reported on the corneal epithelial barrier defect and subsequent development of corneal keratinization in Notch-1 conditional knockout mice (Notch-1 K14-Cre-ERT). We sought to determine if there was a differences in the presentation of the corneal phenotype based on the sex.
10 Male and 10 female conditional knockout mice were treated with 5 consecutive days of intraperitoneal injection of tamoxifen (1mg/20g body weight). We observed each group for the development of cornea epithelial keratinization at 3 and 5 weeks after treatment with tamoxifen. The corneas were also examined histologically and the percentage of corneal keratinization was calculated.
Three weeks after tamoxifen treatment, we observed keratinization in 60% of the male mice (6 out of 10) while female group only had 30% keratization (3 out of 10). By 5 weeks after tamoxifen treatment, still 60% of the male mice had corneal keratinization but only 40% of the female mice had developed this phenotype. Cryosections demonstrated the degree of keratinization in male mice to be more severe than in the females.
Male conditional Notch1 knockout mice developed corneal epithelial disease earlier and more frequently than female mice. This highlights the importance of sex as a biological variable in this phenotype. There are several potential explanations; one might be sex differences in Cre recombinase activity, another might be the tendency for male mice to be more violent and have more trauma to their corneas.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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