Rescue strategy | Nature Reviews Neuroscience


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Access through your institution Buy or subscribe Mutations in SH3 and multiple ankyrin repeat domains protein 3 (_SHANK3_) are associated with several neurodevelopmental disorders, but it is


not known whether correcting SHANK3 levels in the mature CNS would alleviate synaptic impairments in rodents carrying _Shank3_ mutations. Mei _et al_. generated a mouse, lacking


constitutive expression of _Shank3_, in which the gene could be conditionally knocked-in at specific time points. Knock-in of _Shank3_ in these mice during adulthood restored levels of


synaptic proteins and corrected physiological impairments in striatal neurons, and rescued impairments in social behaviour. In a different approach, Bidinosti _et al_. characterized the


dysregulation of phosphoprotein expression that occurs in rat cortical neurons that lack _Shank3_ and showed that the expression of CDC-like kinase 2 (CLK2) was upregulated in these cells.


Pharmacological inhibition of CLK2 corrected synaptic deficits in brain slices from adult mice carrying a mutation in exon 21 of _Shank3_ and rescued impairments in social behaviour in these


mice. Together, these findings suggest that adulthood restoration of SHANK3 levels, or restoration of downstream mediators, may be a useful strategy to alleviate some of the synaptic and


behavioural impairments associated with _SHANK3_ mutations. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to


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customer support REFERENCES * Mei, Y. et al. Adult restoration of _Shank3_ expression rescues selective autistic-like phenotypes. _Nature_ http://dx.doi.org/10.1038/nature16971 (2016) *


Bidinosti, M. et al. CLK2 inhibition ameliorates autistic features associated with SHANK3 deficiency. _Science_ http://dx.doi.org/10.1126/science.aad5487 (2016) Download references Authors *


Fiona Carr View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Carr, F.


Rescue strategy. _Nat Rev Neurosci_ 17, 200 (2016). https://doi.org/10.1038/nrn.2016.31 Download citation * Published: 10 March 2016 * Issue Date: April 2016 * DOI:


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