Transgenes located on the X chromosome have been used to study the mec
hanisms involved in X-chromosome inactivation. Analysis of the transge
nic mouse strain M-TKneo1 carrying a neomycin resistance gene inserted
in the X chromosome showed that, in adult somatic tissues, this trans
gene 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, w
hereas these genes are subject to random inactivation in embryonic tis
sues. It has been suggested that, in the mouse, the extraembryonic tis
sues carry a parental imprint at the time of inactivation. The study o
f the neo transgene expression in extra-embryonic endoderm has shown n
ot only that neo is inactivated but also that, at the RNA level, pater
nal inactivation of the transgene seems essentially complete. The diff
erences between our results and previously obtained results with a mou
se alpha-fetoprotein transgene, which was only inactivated in neonatal
tissues but not in extraembryonic tissues, are discussed.