Knocking out the phenotype

Consistent with the work of Rossi et al. (discussed previously),  another recent paper shows a lack of phenotypic response when knocking out a gene that gives a phenotypic response when knocked down.

Knocking out klf2a does not result in any discernible difference from wild-type (whereas knock-down has been shown to produce a range of cardiovascular phenotypes).

The authors conclude:

In summary, our work shows that even in the face of clear evidence of a potentially disruptive mutation induced in a gene of interest, it is currently very difficult to be certain that this leads to loss-of-function, and hence to be confident about the role of the gene in embryonic development.

Using a knock-down reagent that prevents off-target effects is the best way to be confident about your phenotypes.