Expression of genes encoding neuropeptides, receptors and enzymes in the brain, with emphasis on the hypothalamus, are being studied. We successfully created a knock-out of the vasopressin 1b receptor (V1bR) gene in mice through homologous recombination. These mice are growing normally and we are studying them using a variety of different physiological and behavioral challenges. They are not as aggressive as their wildtype littermates, which presents the opportunity to examine the neurological basis of aggression. They also show mild reduction in social recognition. Various anatomical and physiological parameters are under study currently. We are also studying the vasopressin 1a receptor (V1aR) knockout that, surprising, shows no reduction in aggression. Other aspects of this mouse's phenotype are in early steps of exploration. Double knockouts of the V1aR and V1bR are viable and outward appearances are normal. They will also be studied behaviorally and physiologically. We are also examining the areas of expression of the V1bR gene in the rodent brain by immunohistochemistry, hybridization histochemistry and 2-deoxyglucose uptake. We have made an oxytocin receptor pre-knockout line for conditional control of the expression of that gene. Transgenic mouse lines that express an inducible cre recombinase are being created that will be crossed with the """"""""floxed"""""""" oxytocin receptor lines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002498-15
Application #
6980259
Study Section
(LCMR)
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2004
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Pagani, J H; Zhao, M; Cui, Z et al. (2015) Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2. Mol Psychiatry 20:490-9
Pagani, J H; Williams Avram, S K; Cui, Z et al. (2015) Raphe serotonin neuron-specific oxytocin receptor knockout reduces aggression without affecting anxiety-like behavior in male mice only. Genes Brain Behav 14:167-76
Choi, Ji-Woong; Kang, Sung-Min; Lee, Youngkyun et al. (2013) MicroRNA profiling in the mouse hypothalamus reveals oxytocin-regulating microRNA. J Neurochem 126:331-7
Young, W Scott (2013) Shedding heat on oxytocin. Endocrinology 154:3961-2
Cui, Zhenzhong; Gerfen, Charles R; Young 3rd, W Scott (2013) Hypothalamic and other connections with dorsal CA2 area of the mouse hippocampus. J Comp Neurol 521:1844-66
Pobbe, Roger L H; Pearson, Brandon L; Defensor, Erwin B et al. (2012) Oxytocin receptor knockout mice display deficits in the expression of autism-related behaviors. Horm Behav 61:436-44
Sanek, Nicholas A; Young, W Scott (2012) Investigating the in vivo expression patterns of miR-7 microRNA family members in the adult mouse brain. Microrna 1:11-8
Mok, Stephanie I; Munasinghe, Jeeva P; Young, W Scott (2012) Infusion-based manganese-enhanced MRI: a new imaging technique to visualize the mouse brain. Brain Struct Funct 217:107-14
Roper, Ja; O'Carroll, A-M; Young 3rd, Ws et al. (2011) The vasopressin Avpr1b receptor: molecular and pharmacological studies. Stress 14:98-115
Lee, Heon-Jin; Pagani, Jerome; Young 3rd, W Scott (2010) Using transgenic mouse models to study oxytocin's role in the facilitation of species propagation. Brain Res 1364:216-24

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