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Conventional vs. Conditional Knockout

Last Updated on October 22, 2020 by ingenious

Conventional KO vs Conditional KO for your target gene

Conventional vs. Conditional Knockout Mice – The Superiority of Advanced Conditional Knockout Technologies

There are many reasons why the issue of conventional vs. conditional knockout mouse models is solved through a clear superiority of advanced conditional methods. Traditional knockouts were originally considered the most advanced engineered knockout laboratory mice. Some of the latest techniques in use today, however, allow for far greater accuracy and efficiency when it comes to having a versatile tool for studying human genes. Also, they are ideal for ensuring that many of the most common limitations of conventional knockout techniques can be bypassed entirely.

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The Basics of Conventional and Conditional Knockouts

When it comes to comparing conventional vs. conditional knockout methods, it helps to know the basics. While conventional knockouts were first, involving animal models created with artificially impaired or eliminated genes that are applied to all the tissues of their bodies, conditional knockouts are more advanced, involving gene knockouts that only target specific tissues or organs. For example, in order to study a disease that affects the liver, scientists might use a conditional knockout that eliminates a specific gene only in that specific organ. Their results can then become much more accurate in terms of the drugs and genetic therapies they develop, which could help countless lives in the long run.

The Limitations of Traditional Conventional Knockout Methods

In terms of understanding the limitations of conventional vs. conditional knockout models, it’s important to remember that conventional knockout is a knockout that can affect all cell types. Some cells are required for embryonic development and if important cells are affected by gene knockout during embryo development, a mouse model may never come to fruition due to embryonic lethality. Also, the gene of interest will be knocked out at all times and in all tissues where the gene is active with a conventional knockout. This limits studies on what occurs in the mouse during different stages of activation and deactivation of the gene of interest because in the case of a conventional KO, the gene is always inactivated.

Why Are New Conditional Knockout Techniques so Popular?

When considering conventional vs. conditional knockouts, it’s important to realize that from the start, conditional knockouts had more capabilities than conventional knockouts. With a conditional KO, gene inactivation can occur in a certain tissue type or at a specific time point made possible by mating a loxP mouse with a specific Cre line available in repositories. Traditionally conventional and conditional mouse models were made by manipulating the gene of interest first in embryonic stem cells that would have to be selected and screened for proper targeting, then injected into blastocysts in order to produce live mice. Today, advanced technologies such as CRISPR can be used to inject zygotes directly, eliminating the time-consuming embryonic stem cell work of the traditional approach. Researchers are potentially able to achieve knockout sooner, and sometimes homozygous knockouts can be found right from the start.

The Advantages of Cutting Edge Gene Editing with Conditional Knockouts

More than four years after the initial development of the CRISPR/Cas9 technique, this and other advanced technologies for obtaining conditional knockouts have become more popular and widely used than conventional techniques. Newer technologies allow for simplicity and efficiency, diminishing the time required to obtain modified target genes and enhancing the bioinformatics tools of the past to identify appropriate RNA sequences. When it comes to the battle between conventional vs. conditional knockout models, it’s safe to say that the added flexibility of conditional knockout along with new technological knockout methods favor the easier and more result-driven conditional knockout methods, to the older, traditional techniques of making a conventional knockout.

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