DESCRIPTION:

Strain specific differences in the basal gene expression selected by computing between strains contrast matrix for significantly different probe-sets (selected by ANOVA) using unpaired t-test. Gene expression level was considered to be specific for a particular strain if it was significantly different (p<0.01) in all three contrasts given for the strain.

LABEL:

Striatum B6 vs 129, D2, SWR

SCORE TYPE:

Binary

DATE ADDED:

2017-04-26

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

Korostynski M, Kaminska-Chowaniec D, Piechota M, Przewlocki R

TITLE:

Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes.

JOURNAL:

BMC genomics Jun 2006, Vol 7, pp. 146

ABSTRACT:

BACKGROUND: Mouse strains with a contrasting response to morphine provide a unique model for studying the genetically determined diversity of sensitivity to opioid reward, tolerance and dependence. Four inbred strains selected for this study exhibit the most distinct opioid-related phenotypes. C57BL/6J and DBA/2J mice show remarkable differences in morphine-induced antinociception, self-administration and locomotor activity. 129P3/J mice display low morphine tolerance and dependence in contrast to high sensitivity to precipitated withdrawal observed in SWR/J and C57BL/6J strains. In this study, we attempted to investigate the relationships between genetic background and basal gene expression profile in the striatum, a brain region involved in the mechanism of opioid action. RESULTS: Gene expression was studied by Affymetrix Mouse Genome 430v2.0 arrays with probes for over 39.000 transcripts. Analysis of variance with the control for false discovery rate (q &lt; 0.01) revealed inter-strain variation in the expression of ~3% of the analyzed transcripts. A combination of three methods of array pre-processing was used to compile a list of ranked transcripts covered by 1528 probe-sets significantly different between the mouse strains under comparison. Using Gene Ontology analysis, over-represented patterns of genes associated with cytoskeleton and involved in synaptic transmission were identified. Differential expression of several genes with relevant neurobiological function (e.g. GABA-A receptor alpha subunits) was validated by quantitative RT-PCR. Analysis of correlations between gene expression and behavioural data revealed connection between the level of mRNA for K homology domain containing, RNA binding, signal transduction associated 1 (Khdrbs1) and ATPase Na+/K+ alpha2 subunit (Atp1a2) with morphine self-administration and analgesic effects, respectively. Finally, the examination of transcript structure demonstrated a possible inter-strain variability of expressed mRNA forms as for example the catechol-O-methyltransferase (Comt) gene. CONCLUSION: The presented study led to the recognition of differences in the gene expression that may account for distinct phenotypes. Moreover, results indicate strong contribution of genetic background to differences in gene transcription in the mouse striatum. The genes identified in this work constitute promising candidates for further animal studies and for translational genetic studies in the field of addictive and analgesic properties of opioids. PUBMED: 16772024
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