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  • 2000-2004  (5)
  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 24 (2001), S. 845-867 
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Quantitative differences are observed for most complex behavioral and pharmacological traits within any population. Both environmental and genetic influences regulate such individual differences. The mouse has proven to be a superb model in which to investigate the genetic basis for quantitative differences in complex behaviors. Genetically defined populations of mice, including inbred strains, heterogeneous stocks, and selected lines, have been used effectively to document these genetic differences. Recently, quantitative trait loci methods have been applied to map the chromosomal regions that regulate variation with the goal of eventually identifying the gene polymorphisms that reside in these regions.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Transgenic mice overexpressing either the mouse γ2L or γ2S subunit of the GABAA receptor were generated in a C57BL/6 J × DBA/2 J mixed background and expanded into transgenic lines. Transgenic mice and littermate controls were analysed with respect to altered behaviour indicative of anxiety, motor activity and acute effects of benzodiazepines and alcohol, as well as with regard to altered responses to alcohol withdrawal and acute functional tolerance to alcohol. Biochemical tests assessed flunitrazepam- and ethanol-enhanced 36Cl– flux stimulated by muscimol in cerebellar and cortical microsacs and [3H]-flunitrazepam binding to cerebellar membranes. There were no significant differences in any of these measures between the transgenic and control mice, except in tests of acute functional tolerance to acute injection of ethanol. Compared to controls, mice carrying either the γ2L or γ2S transgene developed significantly less tolerance to the ataxic effects of ethanol. We conclude that acute functional tolerance to ethanol is very sensitive to the amount of GABAA receptor γ2 subunit available (regardless of whether it is γ2L or γ2S) but overexpression of neither subunit isoform alters other behavioural and biochemical phenotypes.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Addiction biology 5 (2000), S. 0 
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The role of γ-PKC in initial sensitivity and in the development of rapid tolerance to the hypothermic effects of ethanol were investigated in γ-PKC null mutant mice. Effects of the single gene mutation were evaluated on three different genetic backgrounds. Null mutants from a C57BL/6J X 129/SvJ mixed genetic background failed to develop rapid tolerance after 4 days of i.p. ethanol injections. However, when the null mutation was introgressed onto a C57BL/6J background for six generations to create a congenic line, the expression of rapid tolerance unexpectedly reoccurred in the null mutant mice. Subsequent outcrossing of the γ-PKC null mutation to a C57BL/6J X 129/SvEvTac mixed background did not restore the no tolerance phenotype. These observations, taken together with similar results reported previously concerning the development of chronic tolerance to ethanol in these same genotypes, 1 indicate that the gene coding for γ-PKC has pleiotropic effects in the expression of both rapid and chronic tolerance to ethanol-induced hypothermia. However, the impact of γ-PKC is modulated by the background genotype. These results stress the necessity of understanding interactions with genetic background when interpreting the effects of single gene mutations on complex behavioral traits.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Behavior genetics 30 (2000), S. 111-121 
    ISSN: 1573-3297
    Keywords: Anxiety ; null mutant mice ; γ-protein kinase C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract To investigate the contribution of the PKCγ isoform of protein kinase C (PKC) in neurochemical pathways regulating anxiety, mice lacking the gene encoding PKCγ were tested with heterozygote and wild-type littermates in three approach-avoidance tests of anxiety. Null mutant mice consistently displayed a decrease in baseline anxiety-related behaviors in the elevated plus-maze, the black/white box, and the mirrored chamber. In the elevated plus-maze, mutant mice entered the open arms significantly more often and spent more time in the open arms of the maze. In the black/white box, transitions between the compartments were greatest in the null mutant mice, and in the mirrored chamber, mutant mice were markedly less anxious with significantly decreased latencies to enter and more time spent in the chamber. Indices of locomotor activity in the mazes and tests of activity in home cages indicated that the reduced anxiety observed in the mutant mice was not due to baseline locomotor activity differences among the genotypes. These results suggest that PKCγ be considered as one factor in the etiology of anxiety, perhaps via its post-synaptic regulation of GABAA and 5-HT2 receptors, two receptors implicated in the neurobiology of anxiety.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Behavior genetics 30 (2000), S. 183-191 
    ISSN: 1573-3297
    Keywords: QTL ; selection ; learning ; fear conditioning ; linkage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract A short-term selection study for contextual fear conditioning was conducted as a confirmational strategy to analyze the chromosomal locations of five previously mapped contextual fear conditioning quantitative trait loci (QTLs). The founding population was a C57BL/6 (B6) × DBA/2 (D2) F2 intercross. High and low lines were selected for three generations based on contextual fear conditioning scores. Fear conditioning was quantified as the percentage of time spent in a “frozen” posture when placed back into the chamber, where a mild footshock and a tone had been paired with exposure to the context 24 h earlier. Allele frequencies of at least three SSLP DNA markers linked to each of the five QTLs were determined in each generation. As the selection progressed, the frequency of D2 alleles decreased in the low line and increased in the high line for chromosomes 1 and 16, while the opposite was observed in chromosomes 2, 3, and 10. The direction of divergence for alleles on these five chromosomes is consistent with the original QTL mapping study. Differences between the lines in D2 allele frequencies were found to be significant for markers on chromosomes 2, 3, and 16 but did not reach significance on chromosomes 1 or 10. In general, the results are in good agreement with our original fear conditioning QTL mapping study and provide further evidence that these QTLs regulate variation in contextual fear conditioning in crosses of B6 and D2 mice.
    Type of Medium: Electronic Resource
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