Drug Discovery
options for the modern obesity epidemic and asso- ciated conditions such as diabetes, metabolic syn- drome, non-alcoholic fatty liver disease and non- alcoholic steatohepatitis. Standard high-fat diets will reproducibly induce weight gain, insulin resis- tance and hyperglycemia in both wildtype B6 mice and GEMs on the B6 background. B6 GEMs are making it possible to identify new targets for obe- sity and diabetes and play an important role in val- idating therapeutic targets.
The B6 in immuno-oncology
Modern immuno-oncology research has seen a resurgence in the use of the B6 in the form of syn- geneic tumour models. These models make it pos- sible to study how the immune system interacts with a tumour in the context of a full complement of immune cells, which is important in identifying and validating new therapeutic targets for immuno-oncology. The B6 has one of the most fully characterised immune systems of any animal, and there is a wide range of analytical tools and genetic models available to interrogate its function. Humanised B6 GEMs make it possible to test human-specific biologic immunotherapies in a syn- geneic context. Furthermore, there is a growing number of engineered tumours developed from tumour GEM models on the B6 background. Thus, the B6 provides one of the most powerful plat- forms for immuno-oncology discovery.
The B6 in microbiome discovery
One of the most important tools in studying the microbiome is the germ-free mouse, which lacks all micro-organisms and is maintained in sterile isola- tors. Germ-free mice are used to study the micro- biome in depth and to discover how microbes affect health and disease. Although any mouse can be made germ-free, the germ-free B6 is rapidly starting to dominate this new microbiome research field. The microbiome is linked to many different diseases, such as immune disorders, obesity and even cancer, and the B6 mouse is one of the best models for studying these. Germ-free B6 mice are making it possible to understand how the micro- biome contributes to these conditions and enabling the development of new therapeutic avenues tar- geting the microbiome.
Conclusions
The B6 is the most important animal model in modern research. Understanding the critical genetic and microbiome factors that affect B6 model performance will aid in the selection of B6 models and improve the success of a research pro-
Drug Discovery World Fall 2017
gramme. From humble beginnings, this little black mouse has been transformed into one of the most useful tools in biomedical research and is being engineered and employed in ever increas- ingly complex applications.
DDW
Dr Philip Dubé is an Applications Scientist at Taconic Biosciences. Dr Dubé has a PhD in Physiology and an Honor’s BSc in Pharmacology from the University of Toronto. He has more than 16 years of experience in the use of rodent models and provides a wide range of knowledge in the application and execution of successful research studies. He specialises in animal models for micro- biome, inflammatory disorders, oncology, immuno-oncology and metabolic disease research; gnotobiotic and germ-free animal models, their care and use; genetics of rodent animal models; and general animal husbandry, care and use.
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