Knockout Mouse Models
Knockout mice are defined as having a certain gene of interest made inoperative, or "knocked out." Often referred to as KO mice, they are used to study gene function and to validate new drugs and treatments. Charles River delivers high-quality, validated knockout mouse models for generating consistent study data which makes research reproducible, and lowers overall study costs. Our end-to-end commitment ensures adherence of project timelines, confidentiality, exclusivity of intellectual property, breeding under VAF Plus® (SOPF) standards, and secure global delivery.
Webinar Series: Transgenic Mouse and Rat Model Creation
Learn more about CRISPR-Cas9* for genome editing, animal model creation, gene therapy, and modelling human disease by watching our webinar series.
Our scientific team works with industry partners who are leaders in the field of functional genomics and molecular engineering. Our combined in vitro and in vivo expertise provides the optimal environment for creating, characterizing, preserving, and distributing your mice.
Types of Knockout Mouse Models
Constitutive Knockout Mice
This model is engineered to carry an inoperative gene. Usually, inactivation of the gene is achieved by the deletion (partial or total) of its sequence, and it is nonfunctional in the entire animal.
Conditional Knockout Mice
These knockout mice allow the deletion of a gene in a tissue- and/or time-specific manner. Often, the conditional KO mouse is achieved through the Cre-lox system. Instead of deleting the critical sequence, it is flanked by loxP sites (termed a floxed sequence). Cre recombinase deletes the sequence between two loxP sites. An inducible or tissue-specific Cre is used to knockout gene function in only that tissue.
RNAi Knockout Mice
RNA interference can reduce the expression of a target gene, without deleting it. Typically this is combined with conditional and/or inducible approaches to reduce expression of the target only under certain conditions in adult animals.
VIDEO: Considerations for Creating Knockout Mice and Other Transgenic Animal Models
Using genetically engineered rodents as models of human disease, have transformed scientific research. Properly designed and validated, they can provide accurate study data, decrease the number of animals used and reduce study costs. Those working with mutant and transgenic mouse models often fall into two categories, academic research institutions looking to decipher the mammalian genome to understand how a specific gene functions and global pharma and biotech companies utilizing models such as knockout mice, in order to validate new drugs and treatments.
00:46 Research employing these models continues to evolve at an incredible pace. How you obtain and maintain them is important because many factors can impact experimental reproducibility and scientific conclusions. The quickest method is to purchase them from a repository or obtain them from a collaborating lab. However, one must consider if these models are an exact fit for your research needs. What is their health status? Could their genetic integrity have been compromised? Could they be carrying the wrong genes? 01:18 Many institutions have set up internal transgenic cores for generating new mouse models. However, they can sometimes be impacted by health status or capacity issues, which can influence project timelines. In addition, institutions may lack the expertise required for specific projects. CRISPR-Cas9 technology has accelerated the creation of knockout mice and other mutant animals. It not only reduces timelines but also allows for flexibility to work with other species such as the rat model, which may be a better fit for certain studies. 01:53 But is CRISPR always the best choice? To answer this question, you should consider how complex the gene modification is. How to detect unexpected CRISPR off and on target effects. For commercial organizations, issues with IP and licensing may result in serious financial ramifications. An effective way to obtain your knockout, knockin or transgenic mice is to work with a qualified external vendor. 02:20 You'll receive advice from experienced scientific teams, utilizing a variety of techniques, strict adherence to project timelines, access to and advice on CRISPR licensing with ownership of intellectual property, a high health status with breeding under VAF+ or SOPF standards and a high degree of model validation and analysis to ensure your new model generates consistent study data. 02:46 Charles River's model creation services provide an optimal environment for generating, characterizing, preserving and distributing your transgenic lines. Our full service portfolio includes custom breeding, embryology services, genetic testing, drug discovery and safety assessment services. With vast experience in the drug development life cycle, you'll have a trusted partner to get you from concept to clinic. Learn how we can help by talking to someone from our scientific team today.
Frequently Asked Questions (FAQs) About Knockout Mice
What are some of the advantages of using knockout mouse models?
The gene knockout method is the simplest approach to reveal fundamental gene functions. Conditional knockout/inductible mice, inducible knockout mice, and knockdown mice can avoid the risk of a lethal phenotype associated with gene inactivation at earlier stages in development and allow for an analysis of gene inactivation effects on adult animals. Furthermore, as 65% of protein coding genes are likely pleiotropic, a conditional knockout mouse simplifies phenotyping analysis by focusing on a specific cell type.
Are there other project considerations?
Disrupting genes can sometimes result in compensation by other members of a multigene family. In these cases, multiple knockouts may be needed to obtain phenotypical effects (e.g., Hox genes). Moreover, it is possible that gene knockouts may fail to produce observable phenotypes in knockout mice, or may produce different characteristics from those observed in humans. Mouse background choice is an important consideration for better mimicking human phenotypes – ask our experts for further advice.
What are the methods used for generating a knockout mouse model?
Depending on your study and objectives, knockout mice can be obtained through:
- ES cell homologous recombination
- Genome-editing nucleases (e.g., CRISPR knockout)
- One-cell embryo direct injection
- ES cell modification
For further information on knockout mice, please see the IKMC (International Knockout Mouse Consortium) website.
- What other services are offered for mouse models?
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The CRISPR Potential in Accelerating Drug Development
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