title: The restructuring of dopamine receptor subtype gene transcripts in c-fos KO mice.
abstract: Although c-Fos protein is one of the principal molecules in intracellular signaling, c-fos gene disruption is associated with alterations in neuronal functions that do not correspond to its importance in function. The aim of the study was to evaluate the changes of dopaminergic system together with acetylcholinesterase (AChE) in c-fos disruption (KO). KO male mice showed an increase in D₁-like receptor (279% of WT) and D₂-like receptor (345% of WT) binding sites in the cortex. On the gene expression level (assessed by real-time PCR), lower quantities of D₁R-mRNA (0.64) and D₅R-mRNA (0.6) were found in females when compared to males in the frontal cortex, higher D₂R-mRNA in the parietal (1.43) and temporal (2.64) cortex and lower AChE-mRNA (0.67). On the contrary, female striatum contained higher level of D₂R-mRNA (1.62) and AChE-mRNA (1.57) but lower level of D₃R-mRNA (0.73). Hypothalamic D₁R-mRNA, D₂R-mRNA and D₄R-mRNA were higher in females (1.38, 1.63, and 1.68, respectively). Disruption of c-fos increased selectively D₅R-mRNA (1.31) in male parietal cortex, D₂R-mRNA (1.72) in male temporal cortex, and cerebellar D₂R-mRNA in both males (1.43) and females (1.42), respectively. In females, we found rather decrease in DR-mRNA. Multiple correlations in mRNA quantities (in WT mice) were found, which changed considerably upon c-fos KO. Main interactions in WT were inter-regional, CNS of KO underwent an extensive restructuring comprising intraregional interactions in the frontal cortex, hypothalamus, and cerebellum. These changes in DR (between others) could be considered as one of the adaptive mechanisms in c-fos KO mice.
authors.affiliation: Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Benes
authors.forename: Boris
authors.initials: B
authors.lastname: Mravec
authors.forename: Olga
authors.initials: O
authors.lastname: Krizanova
authors.forename: Richard
authors.initials: R
authors.lastname: Kvetnansky
authors.forename: Jaromir
authors.initials: J
authors.lastname: Myslivecek
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency*; D012333:RNA, Messenger / Q000378:metabolism; D011954:Receptors, Dopamine / Q000235:genetics* / Q000378:metabolism*; D012737:Sex Factors; D013134:Spiperone / Q000493:pharmacokinetics; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011954:Receptors, Dopamine; C534628:SCH 23390; D014316:Tritium; D013134:Spiperone; D000110:Acetylcholinesterase