title: The restructuring of muscarinic receptor subtype gene transcripts in c-fos knock-out mice.
abstract: Although c-Fos plays a key role in intracellular signalling, the disruption of the c-fos gene has only minor consequences on the central nervous system (CNS) function. As muscarinic receptors (MR) play important roles in many CNS functions (attention, arousal, and cognition), the c-fos knock-out might be compensated through MR changes. The aim of this study was to evaluate changes in the M1-M5 MR mRNA in selected CNS areas: frontal, parietal, temporal and occipital cortex, striatum, hippocampus, hypothalamus and cerebellum (FC, PC, TC, OC, stria, hip, hypo, and crbl, respectively). Knocking out the c-fos gene changed the expression of MR in FC (reduced M1R, M4R and M5R expression), TC (increased M4R expression), OC (decreased M2R and M3R expression) and hippocampus (reduced M3R expression). Moreover, gender differences were observed in WT mice: increased expression of all M1-M5R in the FC in males and M1-M4R in the striatum in females. A detailed analysis of MR transcripts showed pre-existing correlations in the amount of MR-mRNA between specific regions. WT mice showed three major types of cortico-cortical correlations: fronto-occipital, temporo-parietal and parieto-occipital. The cortico-subcortical correlations involved associations between the FC, PC, TC and striatum. In KO mice, a substantial rearrangement of the correlation pattern was observed: only a temporo-parietal correlation and correlations between the FC and striatum remained, and a new correlation between the hypothalamus and cerebellum appeared. Thus, in addition to the previously described dopamine receptor restructuring, the restructuring of MR mRNA correlations reveals an additional mechanism for adaptation to the c-fos gene knockout.
authors: Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. johnbenes@volny.cz
authors: Jan
authors: J
authors: Benes
authors: Boris
authors: B
authors: Mravec
authors: Richard
authors: R
authors: Kvetnansky
authors: Jaromir
authors: J
authors: Myslivecek
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D016762:Genes, fos / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger; D060888:Real-Time Polymerase Chain Reaction; D011976:Receptors, Muscarinic / Q000096:biosynthesis* / Q000235:genetics; D012727:Sex Characteristics; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; D011976:Receptors, Muscarinic