The generation of knock-in mouse models offers access to a variety of GEM models such as: Modeling human SNPs by creating a point mutation in the mouse or rat gene, genetic humanizations where the endogenous gene is replaced by the human gene, and fluorescent reporter models where the expression of a fluorescent protein is driven by endogenous regulatory elements. Depending on the model design, knock-in mice and rats may be used to streamline drug development, assess pharmacokinetic/pharmacodynamic (PK/PD) modeling of novel therapeutics, model human disease and explore pathogenic mechanisms, study basic biology at the whole animal, tissue-, and cell-level, and more. Given Taconic Biosciences' deep toolbox and extensive experience, the range of knock-in mice and rats that we can generate is vast.
At Taconic we generate knock-in mouse models using either CRISPR/Cas9 in embryos or homologous recombination (HR) in embryonic stem cells (ESCs), whereas knock-in rat models are generated using the CRISPR/Cas9 system. Broadly speaking, CRISPR/Cas9 methodology is better suited for short DNA sequence knock-ins (e.g., point mutations, small protein tags, fluorescent reporters) whereas HR in ESCs is better suited for long DNA sequence knock-ins (e.g., genomic replacement humanizations).
Embryonic stem cell-mediated mouse model generation remains the gold standard and best choice for complex projects. The fidelity of this process, along with our extensive experience, allows Taconic to routinely perform the largest genomic insertions in the industry.
Browse the menu below to see examples of how different targeting strategies lead to the generation of several different mouse models.