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 Buck

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)143-147
Number of pages5
JournalAddiction Biology
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2015

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Ethanol
PDZ Domains
Genetic Models
Heterozygote
Alcoholism
Self Administration
Reward
Proteins

Keywords

  • Consumption
  • ethanol
  • MPDZ
  • MUPP1
  • withdrawal

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Pharmacology

Cite this

Novel MPDZ/MUPP1 transgenic and knockdown models confirm Mpdz's role in ethanol withdrawal and support its role in voluntary ethanol consumption. / Milner, Lauren C.; Shirley, Renee L.; Kozell, Laura B.; Walter, Nicole A.; Kruse, Lauren C.; Komiyama, Noboru H.; Grant, Seth G N; Buck, Kari.

In: Addiction Biology, Vol. 20, No. 1, 01.01.2015, p. 143-147.

Research output: Contribution to journalArticle

Milner, Lauren C. ; Shirley, Renee L. ; Kozell, Laura B. ; Walter, Nicole A. ; Kruse, Lauren C. ; Komiyama, Noboru H. ; Grant, Seth G N ; Buck, Kari. / Novel MPDZ/MUPP1 transgenic and knockdown models confirm Mpdz's role in ethanol withdrawal and support its role in voluntary ethanol consumption. In: Addiction Biology. 2015 ; Vol. 20, No. 1. pp. 143-147.
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