"The African naked mole-rat (Heterocephalus glaber) is an unusual rodent species that has evolved physiological strategies to adapt to an extreme ecological niche. It is the only poikilothermic mammal (cold-blooded), has an extraordinarily long life span for its small size (in excess of 30 years) and lives in large colonies organized like those of termites (eusocial). We have shown that naked mole-rats lack physiological attributes thought essential and protective for most other animal species. For example, severe tissue acidosis is life threatening as well as painful and yet naked mole-rats completely lack behavioral sensitivity to acid and sensory neurons are not activated by protons in this species. Here we will identify functionally important naked mole-rat gene variants that may account for aspects of the extreme physiology in this species. We have already identified candidate naked mole-rat-genes whose altered function, compared to other mammals, may account for acid insensitivity, lack of pain sensitization and poikilothermy in this species. These gene variants will be functionally characterized by replacing the mouse gene with a naked-mole rat variant using molecular genetic techniques. In addition we will use next generation sequencing to identify further naked mole-rat gene variants. These studies will allow us to learn how evolution selected for functionally significant gene variants that can radically alter normal physiology in the context of a rodent genome."