The AMF is world-renowned expert in generating genetically engineered mouse models (GEMMs). GEMMs closely mimic human cancer in terms of genetic composition, interactions with other cell types, drug response, and resistance and are therefore indispensable in cancer research. In addition, the AMF keeps track of recent technological developments and tests their usefulness for improving model generation.
The AMF provides a full-service approach covering the design and all hands-on steps such as DNA engineering, ESC manipulation, electroporation and screening of the offspring. All new animal models are housed in a Specific Pathogen Free (SPF) environment. Models are archived by cryopreservation and only recovered when needed, which can reduce the number of animals kept in stock.
Our goal is to help scientists to generate the most optimal animal model for their research. Aspects such as the 3R’s and feasibility of the model play a major role in this process. A detailed overview of all the steps is described in this publication (Generating Modified Mice: A Decision Guide by Ivo J. Huijbers).
Next to the germline GEMMs, we can assist in somatic mouse modeling by designing and generating viral constructs and producing virus particles. For example, lentiviral delivery of sgRNAs in the mammary gland can be used for loss-of function mutations in this specific tissue in mice expressing Cas9 (Annunziato et al. 2016).
We are currently setting up in vivo tissue electroporation in mice and are investigating if we can service the generation of genetically engineered rat models.
Genetically engineered mouse modeling - The methods to modify the mouse genome vary from classic homologous recombination using a targeting construct, to recombinase mediated cassette exchange (RMCE), transposon systems or the CRISPR-Cas9 genome editing technology.
Somatic modeling - Somatic engineered mouse modeling is feasible due to the successful combination of the CRISPR/Cas9 system with efficient delivery systems (viral and non-viral) that vary according to the target organ. Furthermore, we are currently setting up in vivo tissue electroporation procedures enabling an even faster and more flexible generation of somatic models for cancer.
In vitro modeling - We also provide the service to generate in vitro models by manipulating our ESC clones. We have a large collection of validated GEMM-ESC clones re-derived from genetically engineered mouse models. We can design and clone the targeting or exchange constructs and perform all ESC manipulations. Some ESC clones are available through the EMMA repository. These include the well-known models of Anton Berns and Jos Jonkers.