Understanding molecular mechanisms for diabetes and obesity through mouse models
Merkestein M., Cox R., Ashcroft F.
© 2014 S. Karger AG, Basel. Genome-wide association studies have identified several susceptibility genes for diabetes and obesity, whose exact function is often unknown. Mouse models provide a valuable tool for identifying their functional roles and how changes in their expression and/or function can lead to disease. Despite genetic and metabolic differences between mice and humans, the mouse is a good model organism as it breeds rapidly, its genome has been sequenced and it can be easily genetically manipulated. We illustrate the applicability of mouse models to the study of diabetes and/or obesity susceptibility genes using the fat mass- and obesity-associated (FTO) gene. When single-nucleotide polymorphisms in intron one of FTO were first found to be associated with obesity, little was known about the function of FTO. The use of mouse models has confirmed that FTO indeed plays a role in the regulation of energy homeostasis and provided much information about the various phenotypic characteristics it regulates. More detailed models promise much further information. This example underlines the importance of appropriate mouse models in providing insight into the function of other diabetes- and/or obesity-associated genes and the underlying mechanisms by which they cause disease.