Difference Between Conditional and Constitutive Knockout

The key difference between conditional and constitutive knockout is that conditional knockout is the deletion of a gene of interest from a specific tissue or organ while constitutive knockout is the permanent deletion of a gene of interest from the animal.

Mouse is a good analogue for most human biological processes since they share about 99% of similar genes. Knockout mice are useful experimental animals, and they are used in research in order to study different types of cancers and human diseases such as obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, ageing and Parkinson’s disease etc. Knockout mice are genetically modified organisms that have a functionally inactivated a gene of interest. Knockout of gene can be made by replacing it or by inserting an artificial piece of DNA to inactivate it. Knockout mice provide valuable information about the functions of genes. There are two knockout models as constitutive (conventional) and conditional. In constitutive model, the target gene is permanently inactivated in the whole animal for all times. In conditional model, inducible inactivation of gene expression takes place as tissue-specific or temporal manner.

CONTENTS

1. Overview and Key Difference
2. What is Conditional Knockout
3. What is Constitutive Knockout
4. Similarities Between Conditional and Constitutive Knockout
5. Side by Side Comparison – Conditional vs Constitutive Knockout in Tabular Form
6. Summary

What is Conditional Knockout?

Conditional knockout is a model in which a gene of interest is deleted only from a specific tissue or an organ. This model involves timely or tissue-specific deletion of a gene. When compared to constitutive knockout model, conditional knockout model is more advanced. It deletes a gene only in the target organ or tissue. For example, conditional knockout model is used studying a disease that affects the liver (organ). Here, scientists eliminate that particular gene from the liver. Conditional knockout eliminates the side effects of conventional knockout.

Conditional knock out facilitates the knock out genes at a specific developmental stage. It also allows us to study how the knockout of a gene in one tissue affects the same gene in other tissues. This model is often used in order to study human diseases in other mammals. Conditional knockout mouse model can be constructed within 6 to 9 months using CRISPR gene-editing technology.

What is Constitutive Knockout?

Constitutive Knockout model (conventional or whole-body Knockout) is the model in which a target gene is permanently inactivated in the whole animal (in every cell of the organism). Generally, it takes four to six months to construct a constitutive knockout mice model using CRISPR gene-editing technology. However, the time varies depending on the technology used to construct the model.

Compared to conditional knockout model, constitutive knockout is the initially developed model which has side effects. The gene of interest is deleted from all developmental stages. Therefore, the gene expression does not take place throughout the lifetime of the animal. When compared to constitutive knockout, conditional knockout is safe, easier and more results-driven.

What are the Similarities Between Conditional and Constitutive Knockout?

• Conditional and constitutive knockout are two knockout gene models.
• In both models, a gene of interest is eliminated.
• Constructing both models, CRISPR gene-editing technology is widely used.

What is the Difference Between Conditional and Constitutive Knockout?

In conditional knockout, the gene of interest is inactivated in a certain tissue type or at a specific time point. In constitutive knockout, the gene of interest is permanently inactivated for all time. So, this is the key difference between conditional and constitutive knockout. Conditional knockout is more targeted than constitutive knockout. Moreover, conditional knockout is safe and more result-driven than the constitutive knockout.

Below info-graphic lists more differences between conditional and constitutive knockout in tabular form.

Summary – Conditional vs Constitutive Knockout

Knockout mice are useful to study in vivo gene function. They provide insight into a gene’s physiological role in humans. Hence, they are a valuable tool for geneticists to develop therapies to treat genetic diseases. Conditional and constitutive knockout mice are two models. In conditional knockout, a gene of interest is inactivated in a certain tissue type or at a specific time point. In constitutive knockout, a gene of interest is inactivated permanently in all types of tissues in all the time. Thus, this is the key difference between conditional and constitutive knockout. Conditional knockout is more targeted, safe, easier and more results-driven compared to constitutive knockout.

Reference:

1. Hall, Bradford, et al. “Overview: Generation of Gene Knockout Mice.” Current Protocols in Cell Biology, U.S. National Library of Medicine, Sept. 2009, Available here.
2. “Gene Knockout.” Gene Knockout Technology | Gene Knockout Mice | KO First | Crispr Knockout | Shanghai Model Organism, Available here.

Image Courtesy:

1. “Conditional Knockout Mouse”By Yun-Zheng Le – (CC BY-SA 2.5) via Commons Wikimedia
2. “Knockout mouse breeding scheme” By Kjaergaard – Own work (CC BY 3.0) via Commons Wikimedia