title: Novel MPDZ/MUPP1 transgenic and knockdown models confirm Mpdz's role in ethanol withdrawal and support its role in voluntary ethanol consumption.
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.
authors.affiliation: Department of Behavioral Neuroscience, Department of Veterans Affairs Medical Center and Oregon Health & Science University, Portland, OR, USA.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Milner
authors.forename: Renee L
authors.initials: RL
authors.lastname: Shirley
authors.forename: Laura B
authors.initials: LB
authors.lastname: Kozell
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Walter
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Kruse
authors.forename: Noboru H
authors.initials: NH
authors.lastname: Komiyama
authors.forename: Seth G N
authors.initials: SG
authors.lastname: Grant
authors.forename: Kari J
authors.initials: KJ
authors.lastname: Buck
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D020270:Alcohol Withdrawal Seizures / Q000209:etiology / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects*; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D008565:Membrane Proteins; C491750:Mpdz protein, mouse; D000431:Ethanol
keywords: Consumption; MPDZ; MUPP1; ethanol; withdrawal