Recent reports emphasized the role of FOXO family of transcription factors in nervous system homeostasis. Most studies employed primary neuronal cultures, established animal models for neuropathology, or invertebrate models. Demonstration of the normal and pathophysiological function of mammalian FOXO under complex in vivo conditions requires genetic study. Therefore, the conditional knockout mouse is an invaluable platform. Here, we describe the methods of establishing and analyzing nervous system-specific ablation of FOXO isoforms in mice. This chapter offers a detailed method to validate the deletion of Foxo genes in vivo and to study its role in the nervous system. Investigation of FOXO function by using the mouse system may advance our understanding of nervous system aging as well as neurodegenerative diseases.
Keywords: Aging; Brain; FOXO; Immunohistochemistry; Mouse model; Nervous system; Neurodegeneration.