TY - JOUR
T1 - Evaluation of the glutamate decarboxylase genes Gad1 and Gad2 as candidate genes for acute ethanol withdrawal severity in mice
AU - Fehr, Christoph
AU - Rademacher, Brooks L.S.
AU - Buck, Kari J.
N1 - Funding Information:
This study was supported by the Deutsche Forschungsgemeinschaft (Fe 524/1-1), the Department of Veterans Affairs and the NIH grants: R29AA11114 and P50AA10760. We gratefully acknowledge Dr. Gwynn Daniels, Dr. Reneé Shirley, Heather M. Hood, and Matthew T. Reilly for their personal support of the project.
PY - 2003/5
Y1 - 2003/5
N2 - Previous studies in crosses between the C57BL/6J (B6) and the DBA/2J (D2) mice have implicated a role of the genes encoding for the 67- and 65-kDa isoforms of the glutamate decarboxylase (Gad1 and Gad2) in the manifestation and severity of multiple ethanol-related traits such as acute ethanol withdrawal severity [Buck, K.J., Metten, P., Belknap, J.K., Crabbe, J.C., 1997. Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice. J. Neurosci. 17, 3946-3955], ethanol preference [Phillips, T.J., Belknap, J.K., Buck, K.J., Cunningham, C.L., 1998. Genes on mouse chromosomes 2 and 9 determine variation in ethanol consumption. Mamm. Genome 9, 936-941] and ethanol-induced locomotion [Demarest, K., McCaughran Jr., J., Mahjubi, E., Cipp, L., Hitzemann, R., 1999. Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2. J. Neurosci. 19, 549-561]. Strain-specific sequencing experiments as well as gene expression studies in drug-naïve and ethanol-treated D2 and B6 mice were carried out. The Gad1 sequence was similar, the Gad2 cDNA carried only a silent polymorphism (1017 G>C) between both strains. In addition, no significant GAD65 or GAD67 expression differences were detected in either drug-naïve or acute ethanol withdrawn animals by Western blot experiments. Therefore, these results do not support the hypothesis of an involvement of Gad1 or Gad2 in the pathophysiology of acute ethanol withdrawal severity and the other ethanol related traits.
AB - Previous studies in crosses between the C57BL/6J (B6) and the DBA/2J (D2) mice have implicated a role of the genes encoding for the 67- and 65-kDa isoforms of the glutamate decarboxylase (Gad1 and Gad2) in the manifestation and severity of multiple ethanol-related traits such as acute ethanol withdrawal severity [Buck, K.J., Metten, P., Belknap, J.K., Crabbe, J.C., 1997. Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice. J. Neurosci. 17, 3946-3955], ethanol preference [Phillips, T.J., Belknap, J.K., Buck, K.J., Cunningham, C.L., 1998. Genes on mouse chromosomes 2 and 9 determine variation in ethanol consumption. Mamm. Genome 9, 936-941] and ethanol-induced locomotion [Demarest, K., McCaughran Jr., J., Mahjubi, E., Cipp, L., Hitzemann, R., 1999. Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2. J. Neurosci. 19, 549-561]. Strain-specific sequencing experiments as well as gene expression studies in drug-naïve and ethanol-treated D2 and B6 mice were carried out. The Gad1 sequence was similar, the Gad2 cDNA carried only a silent polymorphism (1017 G>C) between both strains. In addition, no significant GAD65 or GAD67 expression differences were detected in either drug-naïve or acute ethanol withdrawn animals by Western blot experiments. Therefore, these results do not support the hypothesis of an involvement of Gad1 or Gad2 in the pathophysiology of acute ethanol withdrawal severity and the other ethanol related traits.
KW - Behavior genetics
KW - Candidate gene
KW - Ethanol
KW - GABA
KW - QTL
KW - Western blotting
KW - Withdrawal
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U2 - 10.1016/S0278-5846(03)00034-4
DO - 10.1016/S0278-5846(03)00034-4
M3 - Article
C2 - 12691782
AN - SCOPUS:0037402997
SN - 0278-5846
VL - 27
SP - 467
EP - 472
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
IS - 3
ER -