Zebrafish p53 knockdowns to suppress apoptosis - co-inject p53 Morpholinos and targeted Morpholinos (Apr/12/2007 )

Steve Ekker has published a new paper describing a particular set of phenotypic alterations in zebrafish embryos that results from knocking down a range of different genes. These phenotypic alterations are caused by apoptosis mediated by p53. Knocking down p53 simultaneous with another targeted gene knockdown can eliminate the apoptotic phenotype and reveal the specific phenotype related to that other targeted knockdown. This has great potential for eliminating artifacts when using embryonic knockdown techniques.

Robu ME, Larson JD, Nasevicius A, Beiraghi S, Brenner C, Farber SA, Ekker SC. p53 activation by knockdown technologies. PLoS Genetics 2007; in press.
http://genetics.plosjournals.org/perlserv/...gen.0030078.eor

Thanks

Bu yong xie -- you're welcome. Let me know if I can help.

An interesting and unsolved part of the p53 discovery is to find the mechanism by which knockdown of some genes causes the p53 mediated apoptosis. What is p53 detecting? There is no apparent similarity shared by all the oligos that cause the apoptotic effect, so it is unlikely that they are all interacting with p53 RNA. Triggering of p53-mediated apoptosis has been shown using several antisense structural types, as described in Ekker et al. (cited in previous post), so it's not specific to the structure of the antisense. It seems there is something about the knockdown of the proteins that causes the p53 apoptotic effect. This "knockdown cascade" effect intrigues me very much, and I hope someone takes up the study -- it could shed light on the mechanism by which p53 acts in its regular functions as a cellular surveillance protein.

- Jon