Genetically modified mice for research on human diseases: A triumph for Biotechnology or a work in progress?

Genetically modified mice are engineered as models for human diseases. These mouse models include inbred strains, mutants, gene knockouts, gene knockins, and ‘humanized’ mice. Each mouse model is engineered to mimic a specific disease based on a theory of the genetic basis of that disease. For example, to test the amyloid theory of Alzheimer’s disease, mice with amyloid precursor protein genes are engineered, and to test the tau theory, mice with tau genes are engineered. This paper discusses the importance of mouse models in basic research, drug discovery, and translational research, and examines the question of how to define the “best” mouse model of a disease. The critiques of animal models and the caveats in translating the results from animal models to the treatment of human disease are discussed. Since many diseases are heritable, multigenic, age-related and experience-dependent, resulting from multiple gene-gene and gene-environment interactions, it will be essential to develop mouse models that reflect these genetic, epigenetic and environmental factors from a developmental perspective. Such models would provide further insight into disease emergence, progression and the ability to model two-hit and multi-hit theories of disease. The summary examines the biotechnology for creating genetically modified mice which reflect these factors and how they might be used to discover new treatments for complex human diseases such as cancers, neurodevelopmental and neurodegenerative diseases.