Knockout, knock-in: what’s the deal? It sounds like they are opposites; are they?
The context
When talking about gene knockout and gene knock-in, we are talking about the initial creation of non-human animals (fruit flies, worms, mice, fish, pigs, etc.) using genetic engineering, then breeding them for multiple generations. Yes, they were originally genetically engineered but only to create the first generation; subsequent generations breed normally. These non-human animals are used for [preclinical or investigational drug] testing.
Aside: I find it ironic that people tend to understand that you cannot modify the upwards of trillions of copies of DNA in a mature non-human animal—i.e., that the only opportunity to modify one’s DNA is before or soon after cell replication begins—but they resist understanding it’s the same in the context of humans. The only way to introduce (or eradicate) a genetic disease to (or from) an animal is to do it before or soon after cell replication begins, whether a human or non-human animal.
Discussion
Gene knockout should mean that DNA was only removed (e.g., to simulate gene loss—not useful for SCA testing). Gene knock-in should mean that DNA was added (e.g., to cause a disease, such as SCA).
I think the term knockout was coined long before knock-in, so some staunchly use the original knockout term to mean what knock-in has come to mean. Some avoid using the newer knock-in term in favor of things like knock out and replace. As such, some use the term knockout animal to refer to a genetically engineered animal with modified DNA.
When people are trying to be correct and modern, they might use the term knock-in (if intended); when they want to use a term that’s been around longer, they stick with knockout.
Here’s an example of traditional usage (knockdown means knock-in).
Here’s an example of modern usage (knock-in is used).
Oh, CRUD
I know from computer science that the basic operations you can perform on a database (i.e., thinking of the genome’s DNA as a database) are Create, Read, Update, and Delete. Since an Update can be implemented as a Delete + Create, I see how any terminology system has weaknesses and therefore ambiguities.
A few other points
Nowadays, you can use CRISPR/Cas9 to create some knock-in animals.
If you knock human DNA into a non-human animal and successfully give it a human trait (such as a disease), that can be called transgenics. We are warned here that knock-in mice and transgenic mice are different in some nebulous way, but then bizarrely knock-in seems to be used to mean knockout.
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