William Christopher Wetsel, PhD


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Associate Professor in Psychiatry and Behavioral Sciences
Assistant Research Professor in Cell Biology
Associate Professor in Neurobiology
Assistant Professor in Medicine
Department / Division:
Psychiatry / Translational Neuroscience
354 Sands Bldg
Durham, NC 27710
Office Telephone:
(919) 684-4574
  • PhD, Massachusetts Institute of Technology, 1983
Research Interests:
Last Updated: 31 December 1997

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.
Representative Publications:
  • Allen, JA; Yost, JM; Setola, V; Chen, X; Sassano, MF; Chen, M; Peterson, S; Yadav, PN; Huang, XP; Feng, B; Jensen, NH; Che, X; Bai, X; Frye, SV; Wetsel, WC; Caron, MG; Javitch, JA; Roth, BL; Jin, J. Discovery of ß-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. Proceedings of the National Academy of Sciences of USA. 2011;108:18488-18493.  Abstract
  • Wang, X; McCoy, PA; Rodriguiz, RM; Pan, Y; Je, HS; Roberts, AC; Kim, CJ; Berrios, J; Colvin, JS; Bousquet-Moore, D; Lorenzo, I; Wu, G; Weinberg, RJ; Ehlers, MD; Philpot, BD; Beaudet, AL; Wetsel, WC; Jiang, YH. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Human Molecular Genetics. 2011;20:3093-3108.  Abstract
  • Deng, JV; Rodriguiz, RM; Hutchinson, AN; Kim, IH; Wetsel, WC; West, AE. MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants. Nature Neuroscience. 2010;13:1128-1136.  Abstract
  • Fukui, M; Rodriguiz, RM; Zhou, J; Jiang, SX; Phillips, LE; Caron, MG; Wetsel, WC. Vmat2 heterozygous mutant mice display a depressive-like phenotype. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27:10520-10529.  Abstract
  • Welch, JM; Lu, J; Rodriguiz, RM; Trotta, NC; Peca, J; Ding, JD; Feliciano, C; Chen, M; Adams, JP; Luo, J; Dudek, SM; Weinberg, RJ; Calakos, N; Wetsel, WC; Feng, G. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature. 2007;448:894-900.  Abstract
  • Sotnikova, TD; Beaulieu, JM; Barak, LS; Wetsel, WC; Caron, MG; Gainetdinov, RR. Dopamine-independent locomotor actions of amphetamines in a novel acute mouse model of Parkinson disease. PLoS biology. 2005;3:e271.  Abstract
  • Srinivasan, S; Bunch, DO; Feng, Y; Rodriguiz, RM; Li, M; Ravenell, RL; Luo, GX; Arimura, A; Fricker, LD; Eddy, EM; Wetsel, WC. Deficits in reproduction and pro-gonadotropin-releasing hormone processing in male Cpefat mice. Endocrinology. 2004;145:2023-2034.  Abstract
  • Gainetdinov, RR; Wetsel, WC; Jones, SR; Levin, ED; Jaber, M; Caron, MG. Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science. 1999;283:397-401.  Abstract