Wegener, S;
Buschler, A;
Stempel, AV;
Kang, SJ;
Lim, C-S;
Kaang, B-K;
Shoichet, SA;
... Schmitz, D; + view all
(2018)
Defective Synapse Maturation and Enhanced Synaptic Plasticity in Shank2 Δex7-/- Mice.
eNeuro
, 5
(3)
, Article e0398-17. 10.1523/ENEURO.0398-17.2018.
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Abstract
Autism spectrum disorders (ASDs) are neurodevelopmental disorders with a strong genetic etiology. Since mutations in human SHANK genes have been found in patients with autism, genetic mouse models are used for a mechanistic understanding of ASDs and the development of therapeutic strategies. SHANKs are scaffold proteins in the postsynaptic density of mammalian excitatory synapses with proposed functions in synaptogenesis, regulation of dendritic spine morphology, and instruction of structural synaptic plasticity. In contrast to all studies so far on the function of SHANK proteins, we have previously observed enhanced synaptic plasticity in Shank2 Δex7-/- mice. In a series of experiments, we now reproduce these results, further explore the synaptic phenotype, and directly compare our model to the independently generated Shank2 Δex6-7-/- mice. Minimal stimulation experiments reveal that Shank2 Δex7-/- mice possess an excessive fraction of silent (i.e., α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, short, AMPA receptor lacking) synapses. The synaptic maturation deficit emerges during the third postnatal week and constitutes a plausible mechanistic explanation for the mutants' increased capacity for long-term potentiation, both in vivo and in vitro. A direct comparison with Shank2 Δex6-7-/- mice adds weight to the hypothesis that both mouse models show a different set of synaptic phenotypes, possibly due to differences in their genetic background. These findings add to the diversity of synaptic phenotypes in neurodevelopmental disorders and further support the supposed existence of "modifier genes" in the expression and inheritance of ASDs.
| Type: | Article |
|---|---|
| Title: | Defective Synapse Maturation and Enhanced Synaptic Plasticity in Shank2 Δex7-/- Mice |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1523/ENEURO.0398-17.2018 |
| Publisher version: | http://doi.org/10.1523/ENEURO.0398-17.2018 |
| Language: | English |
| Additional information: | This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| Keywords: | LTP, PSD, autism, maturation, shank, synapse, Animals, Autism Spectrum Disorder, Disease Models, Animal, Hippocampus, Long-Term Potentiation, Male, Mice, Inbred C57BL, Mice, Knockout, Nerve Tissue Proteins, Receptors, AMPA, Synapses |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > The Sainsbury Wellcome Centre |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10069982 |
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