Several animal models exist to study the role of synaptic receptors in stress and anxiety associated with alcohol abuse. These models will be used by the investigators of this Integrated Neuroscience Initiative on Alcoholism (INIA). Other animal models of interest to INIA investigators do not exist and need to be created. For instance, NR2B knockout mice die shortly after birth due to deficiency in suckling behavior. To bypass this early developmental hurdle, we created an inducible NR2B knockout mouse. This mouse, which exhibit a specific pattern of NR2B deletion in forebrain, is now under investigation by several components of the Initiative. The goals of the Gene-Targeted Mouse Core are to 1) create new animal models using the cre-lox system to allow for inducibility (and some tissue-specificity) of gene deletion and provide simple crossing and PCR genotyping protocols;2) create straight knockout mice from existing ES cell lines and 3) maintain and distribute among INIA investigators breeding pairs of each line. The Core takes advantage of a successful collaboration between the Delpire lab, which has generated several models of cation-chloride cotransporter knockouts and several inducible knockouts, and the existing Vanderbilt University Ingram Cancer Center Transgenic/ES cell Core, which has extensive experience in all aspects of gene targeting and manipulation of mouse embryos. These new mouse line will not only be of use to INIA investigators, but will also be of interest to the broader Neuroscience research community.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1-DD (71))
Program Officer
Grandison, Lindsey
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
Schools of Medicine
United States
Zip Code
Wills, Tiffany A; Baucum 2nd, Anthony J; Holleran, Katherine M et al. (2017) Chronic intermittent alcohol disrupts the GluN2B-associated proteome and specifically regulates group I mGlu receptor-dependent long-term depression. Addict Biol 22:275-290
Radke, Anna K; Jury, Nicholas J; Delpire, Eric et al. (2017) Reduced ethanol drinking following selective cortical interneuron deletion of the GluN2B NMDA receptors subunit. Alcohol 58:47-51
Üner, Aykut; Gonçalves, Gabriel H M; Li, Wenjing et al. (2015) The role of GluN2A and GluN2B NMDA receptor subunits in AgRP and POMC neurons on body weight and glucose homeostasis. Mol Metab 4:678-91
Miller, Oliver H; Yang, Lingling; Wang, Chih-Chieh et al. (2014) GluN2B-containing NMDA receptors regulate depression-like behavior and are critical for the rapid antidepressant actions of ketamine. Elife 3:e03581
McCall, Nora M; Sprow, Gretchen M; Delpire, Eric et al. (2013) Effects of sex and deletion of neuropeptide Y2 receptors from GABAergic neurons on affective and alcohol drinking behaviors in mice. Front Integr Neurosci 7:100
Wills, Tiffany A; Klug, Jason R; Silberman, Yuval et al. (2012) GluN2B subunit deletion reveals key role in acute and chronic ethanol sensitivity of glutamate synapses in bed nucleus of the stria terminalis. Proc Natl Acad Sci U S A 109:E278-87
Wang, Chih-Chieh; Held, Richard G; Chang, Shiao-Chi et al. (2011) A critical role for GluN2B-containing NMDA receptors in cortical development and function. Neuron 72:789-805
Badanich, Kimberly A; Doremus-Fitzwater, Tamara L; Mulholland, Patrick J et al. (2011) NR2B-deficient mice are more sensitive to the locomotor stimulant and depressant effects of ethanol. Genes Brain Behav 10:805-816
Brigman, Jonathan L; Wright, Tara; Talani, Giuseppe et al. (2010) Loss of GluN2B-containing NMDA receptors in CA1 hippocampus and cortex impairs long-term depression, reduces dendritic spine density, and disrupts learning. J Neurosci 30:4590-600