Unraveling molecular, cellular and cognitive defects in the mouse model for mental retardation caused by Rsk2 gene mutation
type: Dataset
description: Coffin–Lowry Syndrome (CLS), an X-linked form of intellectual disability, is caused by mutations of the RPS6KA3 gene encoding the growth factor regulated kinase RSK2. To understand the consequences of RSK2 deficiency in the hippocampus we performed a comparison of the hippocampal gene expression profiles from Rsk2-KO and WT mice. It revealed differential expression of 100 genes, encoding proteins acting in various biological pathways. We further analyzed the consequences of deregulation of one of these genes, Gria2 encoding GluR2, a subunit of the glutamate AMPAR. An abnormal two-fold increased expression of GluR2 was found in the hippocampus of Rsk2-KO mice. Electrophysiology studies showed a reduction of basal AMPAR and NMDAR mediated transmission, in the hippocampus of Rsk2-KO mice. Activity of ERK1/2 was also abnormally increased in the adult hippocampus of Rsk2-KO mice. P-Sp1 level was also significantly higher in RSK2 deficient cells. Together, my results suggested that over expression of GluR2 in RSK2 deficient cells, is caused by increased Sp1 transcriptional activity on the Gria2 gene, which, itself, is the result of ERK1/2 increased signaling.
identifier: NNT: 2012STRAJ112
issued: 2026-05-09T12:40:26.682471
language: en
modified: 2026-05-09T12:40:26.682475
contact point: Organization
  fn: CCSD
keyword: coffin-lowry-syndrome
keyword: creb
keyword: erk
keyword: glutamate-receptor
keyword: gria2
keyword: infoeu-reposemanticsdoctoralthesis
keyword: pc12
keyword: recepteur-glutamate-ampa
keyword: rsk2
keyword: sdvbbmgtplife-sciences-q-biobiochemistry-molecular-biologygenomics-q-biogn
keyword: sp1
keyword: syndrome-de-coffin-lowry
keyword: theses
landing page: https://theses.hal.science/tel-00868704

Unraveling molecular, cellular and cognitive defects in the mouse model for mental retardation caused by Rsk2 gene mutation
type: Distribution
format: HTML
issued: 2026-05-09T12:40:26.684325
modified: 2026-05-09T12:40:26.662765
access URL: https://theses.hal.science/tel-00868704

test_moissonnage_selune
type: Agent