Inactivation of an X-linked transgene in murine extraembryonic and adult tissues.

Transgenes located on the X chromosome have been used to study the mechanisms involved in X-chromosome inactivation. Analysis of the transgenic mouse strain M-TKneo1 carrying a neomycin resistance gene inserted in the X chromosome showed that, in adult somatic tissues, this transgene is subject to X-inactivation and to de novo methylation as other endogenous X-linked genes. During mouse embryogenesis, X-linked genes show a preferential paternal inactivation in extraembryonic tissues, whereas these genes are subject to random inactivation in embryonic tissues. It has been suggested that, in the mouse, the extraembryonic tissues carry a parental imprint at the time of inactivation. The study of the neo transgene expression in extraembryonic endoderm has shown not only that neo is inactivated but also that, at the RNA level, paternal inactivation of the transgene seems essentially complete. The differences between our results and previously obtained results with a mouse alpha-fetoprotein transgene, which was only inactivated in neonatal tissues but not in extraembryonic tissues, are discussed.