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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA013514-10
Application #
8019595
Study Section
Special Emphasis Panel (ZAA1-DD (71))
Program Officer
Grandison, Lindsey
Project Start
2002-01-01
Project End
2012-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
10
Fiscal Year
2011
Total Cost
$312,477
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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, K A; Doremus-Fitzwater, T L; Mulholland, P J et al. (2011) NR2B-deficient mice are more sensitive to the locomotor stimulant and depressant effects of ethanol. Genes Brain Behav 10:805-16