Research reportThe restructuring of dopamine receptor subtype gene transcripts in c-fos KO mice

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.

► Restructuring of D1-D5 dopamine receptor subtype transcripts in c-fos knock-out was found. ► Gender differences in gene expression were discovered. ► Main interactions in WT are interregional. ► In c-fos KO inter-regional interactions vanish in favor of intraregional interactions