Genetically Engineered Mouse Models

Genetically engineered mouse models (GEMMs) have developed into key tools in biomedical research over the past decades. The ability to engineer the mouse genome with high precision makes GEMMs perfectly suitable for studying gene function and disease mechanisms, as well as for drug discovery and target validation.

Reverse genetics approaches have matured beyond the generation of simple loss-of-function (e.g., knockout mice) and gain-of-function (e.g., classical transgenic mice) models into technologies that provide conditional control over the expression of a gene of interest in a spatially and/or temporally regulated manner. Site-specific recombinases (SSRs), such as Cre recombinase and Flp recombinase, provide access to genetically defined cell populations enabling cell type-specific manipulation of gene activity or cellular function. The combination of SSR drivers with floxed/flrted genes, SSR-dependent reporters or other genetic tools (e.g., optogenetics, for further reading see Rein and Deussing, 2012) offers a plethora of possibilities to interrogate the function of genes and neural circuits. The latest establishment of site-specific nucleases (SSNs), such as transcription activator-like effector nucleases (TALENs), as well as RNA-guided nucleases (e.g. CRISPR/Cas system), are currently implemented to expand the engineering tools (for further reading see Deussing 2013).

The GEMMs Core Unit offers support to researchers at the Max Planck Institute of Psychiatry and collaborators for the state-of-the-art design of novel genetic mouse models. Solutions are developed according to individual demands and requirements. To this end, the Core Unit provides expertise which covers the entire process from cloning of suitable targeting vectors to the manipulation of embryonic stem cells or one-cell stage embryos. Moreover, the Core Unit manages the Institute's collection of tool strains including mice carrying different floxed alleles, SSR drivers, reporter lines and other mouse genetic tools. All relevant strain-specific information with respect to mating, genotyping, maintenance and application are readily available via the Core Unit.

The unit provides the following services and support:

  • Strategy design for the generation of genetic mouse models
  • Cloning of suitable targeting vectors
  • Manipulation of embryonic stem cells
  • Establishment and initial validation of novel mouse lines
  • High-throughput genotyping
  • Maintenance of various:
    • floxed lines
    • cell/tissue type-specific SSR drivers
    • reporters (GFP, tomato, LacZ)
    • Cre-inducible optogenetic lines
  • Rederivation by embryo transfer
  • Archiving of mouse lines (cryopreservation)
  • Supply of standard operating procedures (SOPs)
 
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