@article{FischerRaabe2018,
  author    = {Fischer, Matthias and Raabe, Thomas},
  title     = {Animal models for Coffin-Lowry syndrome: RSK2 and nervous system dysfunction},
  series = {Frontiers in Behavioral Neuroscience},
  volume    = {12},
  journal   = {Frontiers in Behavioral Neuroscience},
  number    = {106},
  doi       = {10.3389/fnbeh.2018.00106},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176799},
  year      = {2018},
  abstract  = {Loss of function mutations in the rsk2 gene cause Coffin-Lowry syndrome (CLS), which is associated with multiple symptoms including severe mental disabilities. Despite the characterization of ribosomal S6 kinase 2 (RSK2) as a protein kinase acting as a downstream effector of the well characterized ERK MAP-kinase signaling pathway, it turns out to be a challenging task to link RSK2 to specific neuronal processes dysregulated in case of mutation. Animal models such as mouse and Drosophila combine advanced genetic manipulation tools with in vivo imaging techniques, high-resolution connectome analysis and a variety of behavioral assays, thereby allowing for an in-depth analysis for gene functions in the nervous system. Although modeling mental disability in animal systems has limitations because of the complexity of phenotypes, the influence of genetic variation and species-specific characteristics at the neural circuit and behavioral level, some common aspects of RSK2 function in the nervous system have emerged, which will be presented. Only with this knowledge our understanding of the pathophysiology of CLS can be improved, which might open the door for development of potential intervention strategies.},
  language  = {en}
}
@phdthesis{CabelloGonzalez2018,
  author    = {Cabello Gonz{\´a}lez, Victoria},
  title     = {From behavioral to neurobiological characterization of Rsk2 knockout mice as an animal model for Coffin-Lowry syndrome},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171275},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Coffin-Lowry syndrome is a rare syndromic form of X-linked mental retardation caused by heterogeneous loss-of-function mutations in the gene RPS6KA3 that encodes the RSK2 protein. Clinical features are delayed motor development, small height, progressive skeletal malformations and mental retardation. Rsk2 deficiency affects behavioral, cellular and molecular functions. To characterize and investigate how this deficiency affects these functions, we made a series of experiments using Rsk2-deficient mice as the animal model for Coffin-Lowry syndrome. We applied a battery of behavioral tests and included the use of the IntelliCage for the first time as a behavioral paradigm to study anxiety-like behavior and depression-like behavior in Rsk2-deficient mice. Results from the conventional behavioral tests and from the IntelliCage indicate that Rsk2-deficient mice may have an anti-anxiety and anti-depressive phenotype. We evaluated in Rsk2 deficient mice the relative gene expression of a set of genes coding for proteins related to RSK2 which are involved in fear memory, synaptic plasticity, neurogenesis, learning, emotional behavior and stress. We found gene expression alterations in the prefrontal cortex and striatum. These results suggest that RSK2 may be involved in the expression of the genes. RSK2 is known to be related to monoamine neurotransmitter function. We measured the levels of dopamine, serotonin and noradrenaline/norepinephrine and their metabolites in different brain regions of Rsk2-deficient mice. We found differences in the dopaminergic and noradrenergic systems suggesting an increased or decreased activity of these neurotransmission systems as a result of Rsk2 deficiency. Adult neurogenesis is a form of neuronal plasticity and a multi-step process of cell development. We explored if this form of neuronal plasticity was affected by Rsk2-deficiency. Our results indicate that adult hippocampal neurogenesis is not influenced by lifelong Rsk2 deficiency. It would be worth to analyze in the future other aspects of neuroplasticity. We have confirmed, that behavioral characteristics of Rsk2-deficient mice make them an interesting model to study the Coffin-Lowry syndrome by extending the behavioral characterization on the emotional level. Furthermore, we have extended the characterization of the model on a molecular level, opening new opportunities to study and understand the pathophysiological basis of the Coffin-Lowry syndrome.},
  subject      = {Knockout <Molekulargenetik>},
  language  = {en}
}