Özer, Ilkin Deniz: Analyzing the Role of CyFIP2 in the Mouse Brain. - Bonn, 2020. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-58698
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-58698,
author = {{Ilkin Deniz Özer}},
title = {Analyzing the Role of CyFIP2 in the Mouse Brain},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2020,
month = jun,

note = {An important regulator of neuron outgrowth, growth cone motility and dendritic spine formation is the actin nucleator ARP2/3, a protein complex that functions in forming branched actin networks. ARP2/3 complex activity is regulated by the class I nucleation promoting factor WAVE regulatory complex (WRC). In the brain, a crucial component of the pentameric WRC is the Cytoplasmic Fragile-X Mental Retardation Protein (FMRP) Interacting Protein 2 (CyFIP2) that is highly expressed in neurons. Knockout of the Cyfip2 gene in mice leads to perinatal lethality. When Cyfip2 is conditionally knocked out exclusively in the central nervous system (CNS), the mice fully recapitulate the complete knockout phenotype, thus suggesting a specific role for CyFIP2 in the CNS. Here we present our studies on a viable Cyfip2 conditional knockout mouse model, in which the deletion of the gene occurs at around postnatal day 18 (P18) mainly in hippocampal and cortical glutamatergic neurons.
Upon complete loss of CyFIP2, we observed an increase of the small, dynamic actin filaments with no detectable changes in the stable actin pool. The analysis of excitatory synaptic transmission using patch-clamp recordings as well as Schaffer collateral stimulation recordings showed decreased excitatory synaptic transmission and defects in pre-synaptic vesicle exocytosis in the hippocampus. Using electron microscopy, we also showed reduced pre-synaptic bouton area accompanied by decreased neurotransmitter vesicle density in both Schaffer collaterals and mossy fibers, while post-synaptic densities did not appear significantly altered.
In aged mice lacking CyFIP2, we observed increased dendritic spine number possibly in an attempt to compensate for the defects observed in the pre-synapse. These spines were mostly immature, phenocopying the Fragile-X syndrome mouse model. Lastly, a combination of behavioral tests showed a mild anxiety-like phenotype in Cyfip2 forebrain knockout mice with no defects in working and short-term memory according to Y-maze and novel object recognition experiments, respectively.
Our electrophysiological, morphological and biochemical results together suggest a role of CyFIP2 in the structural maintenance of pre-synaptic terminals and dendritic spine maturation in the adult mouse brain that does not appear to be relevant for neurodegenerative processes, but rather for intellectual disability.},

url = {http://hdl.handle.net/20.500.11811/8416}

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