Abstract
Alcohol dependence (alcoholism) is accompanied by evidence of tolerance, withdrawal (physiological dependence), or compulsive behavior related to alcohol use. Studies of strain and individual differences using animal models for acute physiological dependence liability are useful means to identify potential genetic determinants of liability in humans. Behavioral and quantitative trait analyses were conducted using animal models for high risk versus resistance to acute physiological dependence. Using a two-step genetic mapping strategy, loci on mouse chromosomes 1, 4, and 11 were mapped that contain genes that influence alcohol withdrawal severity. In the aggregate, these three risk markers accounted for 68% of the genetic variability in alcohol withdrawal. Candidate genes in proximity to the chromosome 11 locus include genes encoding the α1, α6, and γ2 subunits of type-A receptors for the inhibitory neurotransmitter, GABA. In addition, suggestive linkage is indicated for two loci on mouse chromosome 2, one near Gad1 encoding glutamic acid decarboxylase, and the other near the E12 locus which influences the seizure phenotype in the neurological mutant strain EI. The present analyses detect and map some of the loci that increase risk to develop physiological dependence and may facilitate identification of genes related to the development of alcoholism. Syntenic conservation between human and mouse chromosomes suggests that human homologs of genes that increase risk for physiological dependence may localize to 1q21-q32, 2q24-q37/11p13, 9p21- p23/1p32-p22.1, and 5q32-q35.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3946-3955 |
| Number of pages | 10 |
| Journal | Journal of Neuroscience |
| Volume | 17 |
| Issue number | 10 |
| State | Published - 1997 |
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Keywords
- ethanol
- GABA(A) receptor
- glutamic acid decarboxylase
- handling-induced convulsions
- physiological dependence
- QTL
- quantitative trait locus
- recombinant inbred strain
- seizure
- selective breeding
- withdrawal
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice. / Buck, Kari; Metten, Pamela; Belknap, John; Crabbe, John Jr.
In: Journal of Neuroscience, Vol. 17, No. 10, 1997, p. 3946-3955.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice
AU - Buck, Kari
AU - Metten, Pamela
AU - Belknap, John
AU - Crabbe, John Jr
PY - 1997
Y1 - 1997
N2 - Alcohol dependence (alcoholism) is accompanied by evidence of tolerance, withdrawal (physiological dependence), or compulsive behavior related to alcohol use. Studies of strain and individual differences using animal models for acute physiological dependence liability are useful means to identify potential genetic determinants of liability in humans. Behavioral and quantitative trait analyses were conducted using animal models for high risk versus resistance to acute physiological dependence. Using a two-step genetic mapping strategy, loci on mouse chromosomes 1, 4, and 11 were mapped that contain genes that influence alcohol withdrawal severity. In the aggregate, these three risk markers accounted for 68% of the genetic variability in alcohol withdrawal. Candidate genes in proximity to the chromosome 11 locus include genes encoding the α1, α6, and γ2 subunits of type-A receptors for the inhibitory neurotransmitter, GABA. In addition, suggestive linkage is indicated for two loci on mouse chromosome 2, one near Gad1 encoding glutamic acid decarboxylase, and the other near the E12 locus which influences the seizure phenotype in the neurological mutant strain EI. The present analyses detect and map some of the loci that increase risk to develop physiological dependence and may facilitate identification of genes related to the development of alcoholism. Syntenic conservation between human and mouse chromosomes suggests that human homologs of genes that increase risk for physiological dependence may localize to 1q21-q32, 2q24-q37/11p13, 9p21- p23/1p32-p22.1, and 5q32-q35.
AB - Alcohol dependence (alcoholism) is accompanied by evidence of tolerance, withdrawal (physiological dependence), or compulsive behavior related to alcohol use. Studies of strain and individual differences using animal models for acute physiological dependence liability are useful means to identify potential genetic determinants of liability in humans. Behavioral and quantitative trait analyses were conducted using animal models for high risk versus resistance to acute physiological dependence. Using a two-step genetic mapping strategy, loci on mouse chromosomes 1, 4, and 11 were mapped that contain genes that influence alcohol withdrawal severity. In the aggregate, these three risk markers accounted for 68% of the genetic variability in alcohol withdrawal. Candidate genes in proximity to the chromosome 11 locus include genes encoding the α1, α6, and γ2 subunits of type-A receptors for the inhibitory neurotransmitter, GABA. In addition, suggestive linkage is indicated for two loci on mouse chromosome 2, one near Gad1 encoding glutamic acid decarboxylase, and the other near the E12 locus which influences the seizure phenotype in the neurological mutant strain EI. The present analyses detect and map some of the loci that increase risk to develop physiological dependence and may facilitate identification of genes related to the development of alcoholism. Syntenic conservation between human and mouse chromosomes suggests that human homologs of genes that increase risk for physiological dependence may localize to 1q21-q32, 2q24-q37/11p13, 9p21- p23/1p32-p22.1, and 5q32-q35.
KW - ethanol
KW - GABA(A) receptor
KW - glutamic acid decarboxylase
KW - handling-induced convulsions
KW - physiological dependence
KW - QTL
KW - quantitative trait locus
KW - recombinant inbred strain
KW - seizure
KW - selective breeding
KW - withdrawal
UR - http://www.scopus.com/inward/record.url?scp=0030969246&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030969246&partnerID=8YFLogxK
M3 - Article
VL - 17
SP - 3946
EP - 3955
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 10
ER -