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

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

doi:10.1111/adb.12087

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

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

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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. Association studies implicate the multiple PDZ domain protein 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 created transgenic (TG) and knock-out heterozygote (Mpdz+/-) mice with increased and decreased Mpdz expression, respectively. Both differ in EW compared to wild-type littermates, providing compelling evidence for an inverse relationship between Mpdz expression and EW severity. We also report data that implicate Mpdz in ethanol reward.

Original language	English (US)
Pages (from-to)	143-147
Number of pages	5
Journal	Addiction Biology
Volume	20
Issue number	1
DOIs	https://doi.org/10.1111/adb.12087
State	Published - Jan 1 2015
Externally published	Yes

Keywords

Consumption
MPDZ
MUPP1
ethanol
withdrawal

ASJC Scopus subject areas

Medicine (miscellaneous)
Pharmacology
Psychiatry and Mental health

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10.1111/adb.12087

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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. Association studies implicate the multiple PDZ domain protein 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 created transgenic (TG) and knock-out heterozygote (Mpdz+/-) mice with increased and decreased Mpdz expression, respectively. Both differ in EW compared to wild-type littermates, providing compelling evidence for an inverse relationship between Mpdz expression and EW severity. We also report data that implicate Mpdz in ethanol reward.",

keywords = "Consumption, MPDZ, MUPP1, ethanol, withdrawal",

author = "Milner, {Lauren C.} and Shirley, {Renee L.} and Kozell, {Laura B.} and Walter, {Nicole A.} and Kruse, {Lauren C.} and Komiyama, {Noboru H.} and Grant, {Seth G.N.} and Buck, {Kari J.}",

note = "Publisher Copyright: {\textcopyright} 2013 Society for the Study of Addiction.",

year = "2015",

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doi = "10.1111/adb.12087",

language = "English (US)",

volume = "20",

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TY - JOUR

T1 - Novel MPDZ/MUPP1 transgenic and knockdown models confirm Mpdz's role in ethanol withdrawal and support its role in voluntary ethanol consumption

AU - Milner, Lauren C.

AU - Shirley, Renee L.

AU - Kozell, Laura B.

AU - Walter, Nicole A.

AU - Kruse, Lauren C.

AU - Komiyama, Noboru H.

AU - Grant, Seth G.N.

AU - Buck, Kari J.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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. Association studies implicate the multiple PDZ domain protein 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 created transgenic (TG) and knock-out heterozygote (Mpdz+/-) mice with increased and decreased Mpdz expression, respectively. Both differ in EW compared to wild-type littermates, providing compelling evidence for an inverse relationship between Mpdz expression and EW severity. We also report data that implicate Mpdz in ethanol reward.

AB - 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. Association studies implicate the multiple PDZ domain protein 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 created transgenic (TG) and knock-out heterozygote (Mpdz+/-) mice with increased and decreased Mpdz expression, respectively. Both differ in EW compared to wild-type littermates, providing compelling evidence for an inverse relationship between Mpdz expression and EW severity. We also report data that implicate Mpdz in ethanol reward.

KW - Consumption

KW - MPDZ

KW - MUPP1

KW - ethanol

KW - withdrawal

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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

Abstract

Keywords

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