title: Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin-Lowry syndrome.
abstract: The Coffin-Lowry syndrome, a rare syndromic form of X-linked mental retardation, is caused by loss-of-function mutations in the hRSK2 (RPS6KA3) gene. To further investigate RSK2 (90-kDa ribosomal S6 kinase) implication in cognitive processes, a mrsk2_KO mouse has previously been generated as an animal model of Coffin-Lowry syndrome. The aim of the present study was to identify possible neurochemical dysregulation associated with the behavioral and morphological abnormalities exhibited by mrsk2_KO mice. A cortical dopamine level increase was found in mrsk2_KO mice that was accompanied by an over-expression of dopamine receptor of type 2 and the dopamine transporter. We also detected an increase of total and phosphorylated extracellular regulated kinase that may be responsible for the increased level of tyrosine hydroxylase phosphorylation also observed. By taking into consideration previously reported data, our results strongly suggest that the dopaminergic dysregulation in mrsk2_KO mice may be caused, at least in part, by tyrosine hydroxylase hyperactivity. This cortical hyperdopaminergia may explain some non-cognitive but also cognitive alterations exhibited by mrsk2_KO mice.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, C.U. Strasbourg, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Marques Pereira
authors.forename: Michael
authors.initials: M
authors.lastname: Gruss
authors.forename: Katharina
authors.initials: K
authors.lastname: Braun
authors.forename: Nicolas
authors.initials: N
authors.lastname: Foos
authors.forename: Solange
authors.initials: S
authors.lastname: Pannetier
authors.forename: André
authors.initials: A
authors.lastname: Hanauer
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D038921:Coffin-Lowry Syndrome / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D015852:Eukaryotic Initiation Factor-2; C496901:Kcnn3 protein, rat; D017448:Receptors, Dopamine D2; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D048049:Extracellular Signal-Regulated MAP Kinases; D004298:Dopamine