The mammalian Daxx gene has been identified in a diverse set of yeast interaction trap experiments. Although a facilitating role for Daxx in Fas-induced apoptosis has been suggested, Daxx's physiologic function remains unknown. To elucidate the in vivo role of Daxx, we have generated Daxx-deficient mice. Surprisingly, rather than a hyperproliferative disorder expected from the loss of a pro-apoptotic gene, mutation of Daxx results in extensive apoptosis and embryonic lethality. These findings argue against a role for Daxx in promoting Fas-induced cell death and suggest that Daxx either directly or indirectly suppresses apoptosis in the early embryo.
Parental genomic imprinting refers to the phenomenon by which alleles behave differently depending on the sex of the parent from which they are inherited. In the ease of the routine transgene RSVIgmyc, imprinting is manifest in two ways: differential DNA methylation and differential expression. In inbred FVB/N mice, a transgene inherited from a male parent is undermethylated and expressed; a transgene inherited from the female parent is overmethylated and silent. Using a series of RSVIgmyc constructs and transgenie mice, we show that the imprinting of this transgene requires a c/s-acting signal that is principally derived from the repeat sequences that make up the 3' portion of the murine immunoglobulin a heavy-chain switch region. Such imprinting is relatively independent of the site of transgene insertion but is influenced by the structure of the transgene itself. Imprinting is also modulated by genetic background. Detailed studies indicate that the paternal allele is undermethylated and expressed in inbred FVB/N mice and in heterozygous F~ FVB/N/C57BI/6J mice but is overmethylated and silent in inbred C57B1/6J mice. Consequently, the FVB/N genome appears to carry alleles of modulating genes that dominantly block methylation and permit expression of the paternally imprinted transgene. Furthermore, our results suggest that overmethylation is the default status of both parental alleles and that the paternal allele can be marked in trans by polymorphic factors that act in postblastocyst embryos.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.