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Mouse Models: Explained

Mouse models are invaluable tools for researchers across many different areas and disciplines. Since the beginning of the modern era of genetically modified mouse models in the early 1980s, the possibilities for creating different kinds of models have expanded every year. It’s now easier than ever to edit mouse DNA, for example to study the effects of a known disease-causing mutation. It’s even possible to fully replace mouse genes with human. Whether you’ve generated mouse models before, or you’d like to learn more about our process here at ingenious targeting laboratory, we have the answers to all of your questions.

History of Mouse Models

Mice were first used in the lab in the early 1900s, after adopting the idea from mouse fanciers who would breed them for certain traits. This made the mouse a suitable model for observing Mendel’s laws of inheritance. Spontaneously occurring mutations were also observed and studied in strains that are still used in experiments today. However, the experimental possibilities were drastically limited compared with what can be achieved now.

Incredible developments in two parallel fields, gene editing and genome sequencing, have resulted in a huge variety of new options for researchers using mouse models. Gene editing, or targeted genetic modification, originally enabled the creation of knockout mice, a common type of mouse model. With new gene editing methods including the CRISPR/Cas9 system, and sequence data from the human and mouse genomes, the creation of more complex mouse models has become routine.

Knockout Mouse Model

To generate a knockout mouse model the sequence of a target gene is changed such that it’s inactivated or “knocked out”. Often this is achieved by deleting part of the gene’s sequence. Over time the methods for making genetic changes have improved and new strategies for knockout have been developed. There are now two main types of knockout mouse model being created, constitutive and conditional, each with their own advantages.

Originally the constitutive knockout strategy was the only available method for making knockout mouse models. With a constitutive knockout the target gene is inactivated in every single cell throughout all points in the animal’s life. This approach has some limitations but also has the benefit of simplicity. To enable greater control as to where and when knockout occurs, the conditional knockout strategy was developed. This is particularly useful when studying a genetic mutation that can be lethal in embryonic development. Experiments using conditional knockout mouse models are more complex, with the advantage of targeting the knockout to specific cell types.

In knockout mouse models a fluorescent reporter gene can be incorporated to provide visual confirmation on a cellular level that the gene has been successfully knocked out. A reporter is particularly valuable for conditional knockout models. New technologies, such as ingenious’ TruView system, provide the clearest confirmation of knockout so you can be confident your experiment went as planned.

CRISPR Mouse Model

CRISPR is undoubtedly the leading technology in gene editing right now, as it enables researchers to target genes and generate models faster than ever before. One major advantage is that strategies using CRISPR/Cas are relatively simple for small insertions, deletions, or replacements. Usually it’s straightforward to make a genetic modification and verify that the process was successful. However, when more complicated strategies are required, the chance of unwanted off-target effects makes it more difficult to validate a new model. In these cases additional screening and breeding are necessary to obtain a CRISPR mouse model with the correct, intended targeting. When employed carefully CRISPR is a powerful method to create knockins, knockouts, point mutations, and more.

How are mouse models generated at ingenious?

ingenious targeting laboratory uses both traditional and cutting edge technologies to generate custom mouse models, which are tailored to our clients’ specifications. This ensures that our clients receive the precisely targeted mouse model they need for their research. Because we have been in business since 1998, we have perfected our methods to ensure that we’ll succeed where others have failed.

Do you have a custom mouse model in mind? Get in touch with ingenious targeting laboratory and we’ll guide you through our simple process, so you can focus on your research.

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