Specific interference with gene function by double-stranded RNA in early mouse development

Abstract

The use of double-stranded (ds) RNA is a powerful way of interfering with gene expression in a range of organisms, but doubts have been raised about whether it could be successful in mammals. Here, we show that dsRNA is effective as a specific inhibitor of the function of three genes in the mouse, namely maternally expressed c-mos in the oocyte and zygotically expressed E-cadherin or a GFP transgene in the preimplantation embryo. The phenotypes observed are the same as those reported for null mutants of the endogenous genes. These findings offer the opportunity to study development and gene regulation in normal and diseased cells.

Inhibition of HIV-1 fusion with small interfering RNAs targeting the chemokine coreceptor CXCR4

“…[1][2][3][4][5] Small temporal RNAs have been well studied in the control of precise developmental events in nematodes. 6 Of note, noncoding RNAs make up 98% of the genome in humans and are now known to act as critical factors in complex regulation cascades of all eukaryotic cells.…”

A morpholino phenocopy of the mouse MOS mutation

“…The use of morpholino oligonucleotides (MO) to suppress translation of targeted genes is proving to be a valuable tool for investigating gene function in zebrafish (Nasevicius and Ekker, 2000) and xenopus embryos (Heasman et al, 2000). In mice, MO phenotypes have not been previously reported; however, RNA interference has been used to phenocopy the mos, E-cadherin, and tissue plasminogen activator genetic mutants (Svoboda et al, 2000;Wianny and Zernicka-Goetz, 2000). To investigate the feasibility of using MO to suppress mouse gene function, we attempted to phenocopy the well-characterized and easily discernable mouse mos -/-phenotype.…”

“…In mos-deficient mice or in mouse oocytes injected with mos double-stranded RNA, approximately 60 -75% of oocytes fail to arrest at metaphase II and undergo parthenogenetic activation (Choi et al, 1996;Colledge et al, 1994;Hashimoto et al, 1994;Wianny and Zernicka-Goetz, 2000). In this study, microinjection of 340 pg of mos MO, 17 pg of mos MO, or 340 pg of control MO into the cytoplasm of germinal vesicle stage mouse oocytes resulted in respective parthenogenetic activation rates of 56, 23, and 0% when scored 20 h after 3-isobutyl-1-methyl-xanthine (IBMX) removal (Fig.…”

Tat-regulated expression of RNA interference: Triggers for the treatment of HIV infection

“…RNAi is a potent inhibitor of targeted gene expression in a wide variety of organisms [1,19,20]. The triggers for RNAi are siRNAs that are processed from long, double-stranded or hairpin RNA precursors and become part of a ribonucleoprotein complex [21,22].…”