Disease susceptibility implications of preferential inactivation of the paternal X chromosome in extraembryonic endoderm of the mouse

Abstract

In the mouse, there is preferential inactivation of the paternally-derived X chromosome in extraembryonic tissues of early embryos, including trophectoderm and primitive endoderm or hypoblast. Although derivatives of these tissue have long been considered to be purely extraembryonic in nature, recent studies have shown that hypoblast-derived cells of the 'extraembryonic' visceral endoderm make a substantial cellular contribution to the definitive gut of the fetus. This raises questions about the eventual fate of these cells in the adult and potential disease implications due to the skewed inactivation of the paternally derived X in females heterozygous for X-linked mutations. Similar lineage studies of this tissue have not yet been done in human embryos but differences in the pattern of X chromosome inactivation between mouse and humans indicates that preferential X inactivation will not be an issue in human embryos. Nonetheless, comparisons between mouse and human will be important because of the widespread use of the mouse as a model system for study of genetics, development and disease.

Keywords: Embryonic lineage; Extraembryonic; Gut endoderm; Human; Mouse; Preferential X inactivation.