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Making Mouse Models That Better Reflect Human Metabolic and Neurological Diseases

In addition to their well known functions in the controlling infections, immune cells and inflammatory reactions play crucial roles in metabolic and neurodegenerative diseases, such as obesity and Alzheimer’s disease. In obesity, adipose tissues become infiltrated by a host of immune cells producing inflammatory molecules that drive insulin resistance. In Alzheimer’s disease, brain microglial cells became activated and contribute to the demise of synapses and neurons.

Mouse models have enabled breakthroughs in our understanding of metabolic regulation and brain function, but it has become increasingly clear that they present many shortcomings when translating observations to humans. Humans are infected with a variety of acute and chronic pathogens over the course of their lives, and pathogen-driven selection has shaped the immune system of humans. The same is true for mice. However, laboratory mice traditionally used for biomedical studies are bred in ultra-hygienic environments, and kept free of specific pathogens.

Recent studies have indicated that pathogen infections are important for the basal level of activation and the function of the immune system. Specifically, altering the living conditions of laboratory mice profoundly affects the cellular composition of the innate and adaptive immune systems, resulting in cellular and molecular  patterns that more closely reflect the immune signatures of adult humans. Consideration of these environmental exposures can potentially improve mouse models of human disease.

 

Fellows involved in this project

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Sweden
 

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Is any information on this page incorrect or outdated? Please notify Ms. Nel-Mari Loock at [email protected].