Evaluation of the glutamate decarboxylase genes Gad1 and Gad2 as candidate genes for acute ethanol withdrawal severity in mice

Christoph Fehr; Brooks L.S. Rademacher; Kari J. Buck

doi:10.1016/S0278-5846(03)00034-4

Evaluation of the glutamate decarboxylase genes Gad1 and Gad2 as candidate genes for acute ethanol withdrawal severity in mice

Christoph Fehr
, Brooks L.S. Rademacher
, Kari J. Buck

Behavioral Neuroscience

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

17 Scopus citations

Abstract

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 In addition, no significant GAD65 or GAD67 expression differences were detected in either drug-naïve or acute ethanol withdrawn animals by Western blot experiments.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.

Original language	English (US)
Pages (from-to)	467-472
Number of pages	6
Journal	Progress in Neuro-Psychopharmacology and Biological Psychiatry
Volume	27
Issue number	3
DOIs	https://doi.org/10.1016/S0278-5846(03)00034-4
State	Published - May 2003

Funding

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.

Funders	Funder number
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	R29AA11114
National Institute of Alcohol Abuse and Alcoholism	P60AA010760
U.S. Department of Veterans Affairs
Deutsche Forschungsgemeinschaft	Fe 524/1-1

Keywords

Behavior genetics
Candidate gene
Ethanol
GABA
QTL
Western blotting
Withdrawal

ASJC Scopus subject areas

Pharmacology
Biological Psychiatry

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10.1016/S0278-5846(03)00034-4

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title = "Evaluation of the glutamate decarboxylase genes Gad1 and Gad2 as candidate genes for acute ethanol withdrawal severity in mice",

abstract = "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-na{\"i}ve 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-na{\"i}ve 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.",

keywords = "Behavior genetics, Candidate gene, Ethanol, GABA, QTL, Western blotting, Withdrawal",

author = "Christoph Fehr and Rademacher, \{Brooks L.S.\} and Buck, \{Kari J.\}",

note = "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. Rene{\'e} Shirley, Heather M. Hood, and Matthew T. Reilly for their personal support of the project.",

year = "2003",

month = may,

doi = "10.1016/S0278-5846(03)00034-4",

language = "English (US)",

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pages = "467--472",

journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",

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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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JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Evaluation of the glutamate decarboxylase genes Gad1 and Gad2 as candidate genes for acute ethanol withdrawal severity in mice

Abstract

Funding

Keywords

ASJC Scopus subject areas

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