My laboratory uses genetically-modified mice to study the roles that certain genes and gene products play in the expression of abnormal neuroendocrine, neurological, and psychiatric responses. Traditionally, an identification of neuroendocrine dysfunction has involved biochemical analyses of hormonal responses, those for neurological disorders have relied upon behavioral and postmortem analyses, and those for psychiatric conditions have depended upon phenomenology. The advent of gene manipulation in mice has permitted specific genes to be targeted for disruption, mutation, and/or overexpression in the whole organism or in selected regions or cells in the nervous and other systems. In this way, primary and secondary effects of a given gene manipulation can be related to various neuroendoctine, neurological, or psychiatric conditions in humans. As the Director of the Mouse Behavioral and Neuroendocrine Analysis Core Facility at Duke University (http://sites.duke.edu/mousebehavioralcore/), we have neurobehaviorally phenotyped many different lines of inbred and mutant mice for investigators at Duke and at other research institutions. As a consequence, we have helped to develop many different mouse genetic models of neuroendocrine and neuropsychiatric illness. Following the development of mouse models, we have worked with various investigators to identify the molecular and cellular basis of the neuroendocrine and/or behavioral abnormalities. We are working also with medicinal chemists and certain pharmacological/biotechnological companies to identify novel compounds that will ameliorate abnormal responses in the mutant mice. Some of these preclinical studies are now forming a basis for clinical trials in humans.
