MCCAMouse Clinic for Cancer and Aging research

Contact details: J.M.M. Jonkers/Gerald de Haan/ Ronald van Os
Plesmanlaan 121 1066 CX Amsterdam

The aging population in developed countries leads to rapid increase in cancer incidence and other aging-related disorders. To accelerate cancer and aging research and to contribute to the theme of ‘healthy aging’, the Netherlands Cancer Institute (NKI) and the European Research Institute for the Biology of Aging (ERIBA) have established a Mouse Clinic for Cancer and Aging research (MCCA). The MCCA will accelerate development of realistic mouse models that will be used for developing new therapies against cancer and aging-related diseases. The goal of the Aging Facility within the MCCA is three-fold. First, the Facility will be able to provide aged mice of several routinely used strains to the research community. Second, the Facility will generate a biobank in which a wide variety of tissues derived from aged mice will be stored and will be made available to the community. Third, investigators that wish to age custom-made genetically modified mice to search for age-dependent phenotypes can use the Facility for aging/lifespan studies

The mouse is an excellent model system for studying the role of genetic and environmental factors in cancer and aging in an intact organism. Studies with genetically engineered mouse models (GEMMs) of human disease have resulted in important breakthroughs in our understanding of the molecular basis of cancer and aging. The Netherlands has a leading position in Europe in the development and use of GEMMs for cancer and aging-related research. To maintain and expand this prominent role, the Netherlands Cancer Institute (NKI) and the European Research Institute for the Biology of Aging (ERIBA) have established as part of the National Roadmap for Large-Scale Research Facilities a Mouse Clinic for Cancer and Aging research (MCCA).
The central mission of the MCCA is to facilitate the development and application of advanced mouse models for cancer and aging research. The MCCA houses three facilities:
• A Transgenic facility for efficient and rapid generation of GEMMs of human cancer and aging syndromes. This facility has established methods for efficient derivation of embryonic stem cell (ESC) lines from existing GEMMs. These so-called GEMM-ESC lines can be used for rapid introduction of additional genetic modifications and on-demand generation of mice with complex genotypes tailored to the needs of cancer and aging-related research. The Transgenic facility has also established methods for rapid generation of novel GEMMs by CRISPR/Cas9-mediated introduction of targeted mutations in zygotes or GEMM-ESC lines.
• A Mouse Cancer Clinic for (i) preclinical pharmacological studies with new drugs; (ii) tumor intervention studies, including genetic interventions (using RNA interference or CRISPR/Cas9 technology), radiotherapy, chemotherapy and targeted therapy with small molecules; (iii) imaging of disease development, progression and therapy response in advanced mouse models of human cancer.
• An Aging & Phenotyping facility for (i) age-dependent phenotyping and lifespan studies in wildtype mice and GEMMs; (ii) production and distribution of aged mice from commonly used inbred strains; (iii) biobanking and distribution of tissues from aged mice. The Aging & Phenotyping facility operates in close partnership with Brains-on-Line, a company that performs phenotyping studies for major pharmaceutical companies, and is a strategic partner of the Shared Aging Research Models (ShARM) network for biobanking and distribution of surplus tissues from aged mice to the research community.
The MCCA Mouse Cancer Clinic has been constructed as a negative-barrier unit, allowing external investigators to enter the facility without restrictions. This open-access policy also stimulates interactions between individual research groups from The Netherlands and other European countries. The MCCA is the Dutch national partner of the European INFRAFRONTIER Research Infrastructure. The facilities and services of the MCCA are complementary to those of the other INFRAFRONTIER partners. As such, the MCCA is unique within Europe.
The tissue biobank and the GEMM-ESC technology also result in a reduction and refinement of animal use. The MCCA therefore fulfills three important societal needs: (i) improving the treatment of cancer, (ii) debilitating diseases of elderly and (iii) maximizing the information that can be obtained from experiments with as few animals as possible.

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