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Novel MPDZ / MUPP1 transgenic and knockdown models confirm Mpdz 's role in ethanol withdrawal and support its role in voluntary ethanol consumption
Author(s) -
Milner Lauren C.,
Shirley Renee L.,
Kozell Laura B.,
Walter Nicole A.,
Kruse Lauren C.,
Komiyama Noboru H.,
Grant Seth G. N.,
Buck Kari J.
Publication year - 2015
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12087
Subject(s) - knockout mouse , gene knockdown , genetically modified mouse , ethanol , transgene , heterozygote advantage , medicine , psychology , biology , endocrinology , gene , genetics , receptor , biochemistry , allele
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.