Knockdown vs Knockout

Genetics as it applies to evolution, molecular biology, and medical aspects.

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Exkalibur
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Knockdown vs Knockout

Post by Exkalibur » Mon Jun 15, 2015 2:54 am

Hi,

Just wanted to ask in which situations would you use each?

Thanks in advance.

Exkalibur

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jonmoulton
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Re: Knockdown vs Knockout

Post by jonmoulton » Mon Jun 15, 2015 2:48 pm

There are many considerations. Here are a few.

For a one-time heritable change that will yield a model organism line you can use for years, go with a knockout.

If you are targeting an embryonic lethal gene, you will probably need to use a knockdown. You can either use a reduced dose of the knockdown agent, leading to partial loss of target gene expression, or use a knockdown agent that can be dosed or activated after the period of embryonic lethality.

For a dose-response study of partial to complete loss of the target gene expression, you would need a knockdown.

Knockouts can cause changes in expression of non-target genes as an organism adapts to the loss of the targeted gene. These might include physiological and epigenetic changes as well as, over generations, selection for compensatory mutation. Knockdowns cause fairly rapid changes, on a shorter time scale than knockouts.

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Re: Knockdown vs Knockout

Post by jonmoulton » Tue Jul 21, 2015 6:18 pm

Here is some very recent information about knockdowns versus knockouts. Genetic compensation, as adjustments in gene expression to ease the impact of a deleterious mutation, are observed by this group in knockout animals but not knockdown animals.

Rossi A, Kontarakis Z, Gerri C, Nolte H, Hölper S, Krüger M, Stainier DYR. Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature. 2015;[Epub ahead of print] doi:10.1038/nature14580
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14580.html

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Post by Fornita » Wed May 18, 2016 3:01 am

Easily speaking, knock-down for short time, transient change, you reduce, maybe, 50% the effect of the gene. Knock-out for inherit change, for longer time, you reduce the effect of the gene to 0%.
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