Rats are an ideal animal model for human disease research – compared to mice, rats are physiologically, morphologically, and genetically closer to humans – as covered in our recent Technical Bulletin. Since the first targeted knockout (KO) rat was developed in 2010, significant progress has been made in their use as experimental model animals in basic research, drug screenings, and preclinical drug evaluations. Considering the advantages that rats provide for human disease research and recent advancements in gene editing among the species, conditional knockout (cKO) rat models have quickly become an indispensable tool for biomedical research, preclinical and clinical studies.
With the enhanced control of rat embryos and the use of CRISPR-Pro technology, the scope of applications for rats as experimental model animals in basic research, drug screenings, and preclinical drug evaluations has expanded. However, in regard to the Cre-LoxP system – an important conditional gene expression construct, also known as flox or gene floxing - the application of rats has been seriously hindered due to the limited availability of Cre driver rat strains. Comparatively, the Cre-LoxP system has been widely used in mice, and many genes have corresponding LoxP mice, as well as abundant Cre mouse resources with specific promoters. However, due to the delayed development of gene-editing technology in rats, there are much lower numbers of LoxP or Cre rats connected to a tissue-specific promoter compared to those that are available for mice.
In Cyagen’s exclusive White Paper, our experts analyze the pros and cons of two approaches used in creating cKO rat models – Cre-Lox recombination (gene floxing) and viral vector expression systems, such as adeno-associated virus (AAV) – to help guide their optimal use for your research plans.
Outline of Contents
- Creating a Comprehensive Cre Repository
- Developing Conditional Rats Using Cre-Lox Recombination
- Developing Conditional Rats Using Viral Vector Expression Systems
- Advantages of Adeno-associated Virus for In Vivo Gene Modification
- Combining AAV with Cre-LoxP for Conditional Model Generation
- Disadvantages of AAV-mediated Conditional Gene Editing
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References
- Dietrich, M.R., R.A. Ankeny, and P.M. Chen, Publication trends in model organism research. Genetics, 2014. 198(3): p. 787-94.
- Haery, L., et al., Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation. Front Neuroanat, 2019. 13: p. 93.
- Tsien, J.Z., Cre-Lox Neurogenetics: 20 Years of Versatile Applications in Brain Research and Counting. Front Genet, 2016. 7: p. 19.
- Meek, S., T. Mashimo, and T. Burdon, From engineering to editing the rat genome. Mamm Genome, 2017. 28(7-8): p. 302-314.
- Balakrishnan, B. and G.R. Jayandharan, Basic biology of adeno-associated virus (AAV) vectors used in gene therapy. Curr Gene Ther, 2014. 14(2): p. 86-100.
- Kim, H., et al., Mouse Cre-LoxP system: general principles to determine tissue-specific roles of target genes. Lab Anim Res, 2018. 34(4): p. 147-159.
About Cyagen
In under 15 years since its founding, Cyagen has become a leading provider of custom mouse and rat models – delivering over 78,000 models to researchers worldwide and receiving over 6,200 peer-reviewed citations. Cyagen provides researchers from around the world with transgenic, knockout, knockin, conditional knockout models and also offers a comprehensive series of stem cell products for research use, including cell lines, media, and differentiation kits. From vector and strategy design to animal model creation, cryopreservation, and breeding, Cyagen offers complete outsourcing for all animal model needs.
