Decreased Ethanol Sensitivity and Tolerance Development in γ‐Protein Kinase C Null Mutant Mice Is Dependent on Genetic Background

Bowers, Barbara J.; Owen, Elizabeth H.; Collins, Allan C.; Abeliovich, Asa; Tonegawa, Susumu; Wehner, Jeanne M.

doi:10.1111/j.1530-0277.1999.tb04127.x

Cited by 84 publications

(45 citation statements)

References 51 publications

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“…These modifier genes are often completely unlinked to the targeted locus but are closely related to its function. For example, mice null for ␥-protein kinase C showed a marked difference in sensitivity and tolerance to ethanol solely depending on the genetic background (11). This issue is compounded by the desired intercrossing of several modified lines which may have been generated on genetically distinct backgrounds.…”

Section: Conventional Germ Line Gene-targetingmentioning

confidence: 99%

Of mice and models: improved animal models for biomedical research

Bockamp

Maringer

Spangenberg

et al. 2002

Physiological Genomics

147

109

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The ability to engineer the mouse genome has profoundly transformed biomedical research. During the last decade, conventional transgenic and gene knockout technologies have become invaluable experimental tools for modeling genetic disorders, assigning functions to genes, evaluating drugs and toxins, and by and large helping to answer fundamental questions in basic and applied research. In addition, the growing demand for more sophisticated murine models has also become increasingly evident. Good state-of-principle knowledge about the enormous potential of second-generation conditional mouse technology will be beneficial for any researcher interested in using these experimental tools. In this review we will focus on practice, pivotal principles, and progress in the rapidly expanding area of conditional mouse technology. The review will also present an internet compilation of available tetracycline-inducible mouse models as tools for biomedical research ( http://www.zmg.uni-mainz.de/tetmouse/ ).

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Section: Conventional Germ Line Gene-targetingmentioning

confidence: 99%

Of mice and models: improved animal models for biomedical research

Bockamp

Maringer

Spangenberg

et al. 2002

Physiological Genomics

147

109

View full text Add to dashboard Cite

show abstract

“…This breeding strategy produces homozygous mutant, heterozygous, and homozygous wild-type genotypes within a single litter, thereby providing wild-type littermate controls for each experiment. The PKCγ mutation is maintained in a heterozygous condition on C57BL/6 and 129/S6 inbred strains because homozygous null mutant mice do not survive on the C57BL/6 background (Bowers et al, 1999). All mice were genotyped prior to testing using DNA analysis of tail DNA as described previously (Bowers and Wehner, 2001).…”

Section: Animalsmentioning

confidence: 99%

Regulation of 5-HT2A/C receptors and DOI-induced behaviors by protein kinase Cγ

Bowers

Miyamoto‐Ditmon

Wehner

2006

Pharmacology Biochemistry and Behavior

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Protein kinase C γ (PKCγ) null mutant mice demonstrate increased behavioral impulsivity and ethanol consumption. Pharmacological studies have shown that 5-HT 2A/C receptors modulate impulsivity and ethanol consumption in rodents and that PKC can regulate 5-HT 2A/C receptors. To determine whether PKCγ plays a selective role in 5-HT 2A/C receptor regulation, biochemical and behavioral experiments were performed in PKCγ mutant and wild-type mice. DOI-stimulated phosphoinositol hydrolysis and [ 125 I]-DOI saturation binding in the PFC, and quantitative autoradiography of [ 125 I]-DOI binding sites in 15 brain regions were analyzed. DOI-induced head twitch responses (HTR) were measured in naïve mice after an acute 2.5 mg/kg injection of DOI. Results indicated that DOI-induced HTR was significantly greater in mutant mice compared to wildtype mice. Results of the phosphoinositol hydrolysis, membrane binding, and autoradiography experiments indicated that in mutant mice, increased HTR was associated with increased 5-HT 2A/C receptor function in the PFC, but not increased receptor number or affinity suggesting that PKCγ regulates receptor function but not receptor number. These data support a role for 5-HT 2A/C receptors in the PFC in mediating some of the behavioral differences observed between PKCγ mutant and wild-type mice.

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“…Bowers et al (Bowers et al, 1999) found that the impact of a null mutation of the γ-protein kinase C gene on initial sensitivity to ethanol was modulated by the background genotype of the mouse strain examined. In some strains, the "no tolerance" phenotype was expressed as expected while in other strains, the "no tolerance" phenotype was not expressed.…”

Section: Introductionmentioning

confidence: 99%

Altered hippocampal circuit function in C3H α7 null mutant heterozygous mice

et al. 2008

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The α7 subtype of nicotinic receptor is highly expressed in the hippocampus where it is purported to modulate release of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). The α7 receptormediated release of GABA is thought to contribute to hippocampal inhibition (gating) of response to repetitive auditory stimulation. This hypothesis is supported by observations of hippocampal auditory gating deficits in mouse strains with low levels of hippocampal α7 receptors compared to strains with high levels of hippocampal α7 receptors. The difficulty with comparisons between mouse strains, however, is that different strains have different genetic backgrounds. Thus, the observed interstrain differences in hippocampal auditory gating might result from factors other than interstrain variations in the density of hippocampal α7 receptors. To address this issue, hippocampal binding of the α7 receptor-selective antagonist α-bungarotoxin as well as hippocampal auditory gating characteristics were compared in C3H wild type and C3H α7 receptor null mutant heterozygous mice. The C3H α7 heterozygous mice exhibited significant reductions in hippocampal α7 receptors levels and abnormal hippocampal auditory gating compared to the C3H wild type mice. In addition, a general increase in CA3 pyramidal neuron responsivity was observed in the heterozygous mice compared to the wild type mice. These data suggest that decreasing hippocampal α7 receptor density results in a profound alteration in hippocampal circuit function.

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Decreased Ethanol Sensitivity and Tolerance Development in γ‐Protein Kinase C Null Mutant Mice Is Dependent on Genetic Background

Cited by 84 publications

References 51 publications

Of mice and models: improved animal models for biomedical research

Of mice and models: improved animal models for biomedical research

Regulation of 5-HT2A/C receptors and DOI-induced behaviors by protein kinase Cγ

Altered hippocampal circuit function in C3H α7 null mutant heterozygous mice

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