Generation and characterization of a mouse model of conditional knockout in the endometrial epithelium.

Chromatin remodeling plays an integral part in endometrial homeostasis, having roles in the maintenance of cell identity, epithelial integrity, and prevention of endometrial disease. Chromodomain-helicase-DNA-binding protein 4 () is a chromatin remodeling protein and member of the NuRD complex, which predominantly represses transcription. is mutated in endometrial carcinoma, with most mutations leading to loss of function. has been identified as a tumor suppressor and regulator of stemness in endometrial carcinoma cells, but little is known about the tissue-specific roles of in the endometrial epithelia We generated a conditional floxed allele and combined it with to drive loss in the endometrial epithelium. Consistent with previous reports, expression is absent in the oviducts, ovaries, and kidneys, and it shows variegated expression within the endometrial epithelium. Loss of CHD4 was confirmed by immunohistochemistry, and stained cells were quantified to determine the percentage of endometrial epithelial cells with and without CHD4. Compared to the glandular epithelium, the extent of CHD4 loss was higher in the luminal epithelium and unaffected by age. Mice with conditional knockout of had normal endometrial histology. A 6-month breeding trial was performed to assess the functional effects of endometrial epithelial loss on fertility. No difference in litter size, mean number of pups per litter per dam, or pup weight was found between genotypes. These findings demonstrate that conditional loss using is not sufficient to alter the structure and function of the endometrial epithelium or drive tumorigenesis. As is frequently co-mutated with other cancer driver genes such as , , and , future mouse modeling efforts emulating patient mutational profiles might provide insight into the role of in endometrial carcinoma.