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Novel MPDZ/MUPP1 transgenic and knockdown models confirmMpdz's role in ethanol withdrawal and support its role in voluntary ethanol consumption

Year: 2013
Type: article
Abstract: Association studies implicate multiple PDZ domain protein (MPDZ/MUPP1) sequence and/or expression in risk for alcoholism in humans and ethanol withdrawal (EW) in mice, but confirmation has been hindered by the dearth of targeted genetic models. We report the creation of transgenic (MPDZ-TG) and knockout heterozygote (Mpdz(+/-) ) mice, with increased (2.9-fold) and decreased (53%) target expression, respectively. Both models differ in EW compared with wild-type littermates (P ≤ 0.03), providing compelling evidence for an inverse relationship between Mpdz expression and EW severity. Additionally, ethanol consumption is reduced up to 18% (P = 0.006) in Mpdz(+/-) , providing the first evidence implicating Mpdz in ethanol self-administration.
DOI: 10.1111/adb.12087
Authors: Lauren C. Milner, Renee L. Shirley, Laura B. Kozell, Nicole A. Walter, Lauren C. Kruse, Noboru H. Komiyama, Seth G. N. Grant, Kari J. Buck
Language: English
Open Access status: green
Funders: U.S. Department of Veterans Affairs, Burroughs Wellcome Fund, Wellcome Trust, Seventh Framework Programme, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse
Awards: G236021082, G3470773076, Genetic Vulnerability to Drugs of Abuse, G4986090938, Mechanisms of neurotoxicity of amyloid aggregates., G74635121, MPDZ and New Therapeutic Targets in Translational Alcohol Behaviors, BIOLOGICAL BASES OF ALCOHOLISM, Behavioral Genomics of Alcohol Neuroadaptation
OpenAlex ID: W2143428374
FWCI: 1.633
Cites: 19
Cited by: 23
Related to: 10