Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2

@article{Schmeisser2012AutisticlikeBA,
  title={Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2},
  author={Michael J. Schmeisser and Elodie Ey and Stephanie Wegener and Juergen Bockmann and A Vanessa Stempel and Angelika Kuebler and Anna-Lena Janssen and Patrick T. Udvardi and Ehab Shiban and Chris Spilker and Detlef Balschun and Boris V. Skryabin and Susanne tom Dieck and Karl-Heinz Smalla and Dirk Montag and Claire S Leblond and Philippe Faure and Nicolas Torquet and Anne-Marie Le Sourd and Roberto Toro and Andreas Martin Grabrucker and Sarah A. Shoichet and Dietmar Schmitz and Michael R. Kreutz and Thomas Bourgeron and Eckart D. Gundelfinger and Tobias M. Boeckers},
  journal={Nature},
  year={2012},
  volume={486},
  pages={256-260}
}
Autism spectrum disorders comprise a range of neurodevelopmental disorders characterized by deficits in social interaction and communication, and by repetitive behaviour. Mutations in synaptic proteins such as neuroligins, neurexins, GKAPs/SAPAPs and ProSAPs/Shanks were identified in patients with autism spectrum disorder, but the causative mechanisms remain largely unknown. ProSAPs/Shanks build large homo- and heteromeric protein complexes at excitatory synapses and organize the complex… 

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References

SHOWING 1-10 OF 42 REFERENCES
Shank3 mutant mice display autistic-like behaviours and striatal dysfunction
TLDR
It is shown that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction and a critical role for SHANK3 in the normal development of neuronal connectivity is demonstrated.
Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3.
TLDR
It is concluded that loss of major Shank3 species produces biochemical, cellular and morphological changes, leading to behavioral abnormalities in mice that bear similarities to human ASD patients with SHANK3 mutations.
Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication
TLDR
The results are consistent with altered synaptic development and function in Shank3 haploinsufficiency, highlighting the importance of Shank3 in synaptic function and supporting a link between deficits in synapse function and neurodevelopmental disorders.
Sociability and motor functions in Shank1 mutant mice
A Neuroligin-3 Mutation Implicated in Autism Increases Inhibitory Synaptic Transmission in Mice
TLDR
It is suggested that increased inhibitory synaptic transmission may contribute to human ASDs and that the R451C knockin mice may be a useful model for studying autism-related behaviors.
Inherited and de novo SHANK2 variants associated with autism spectrum disorder impair neuronal morphogenesis and physiology
TLDR
To demonstrate that R462X when expressed in mouse can be linked to physiological effects, it is demonstrated that principal neurons of mice expressing rAAV-transduced SHANK2-R462X present a specific, long-lasting reduction in miniature postsynaptic AMPA receptor currents, with an impact on the penetrance of ASD.
Behavioral profiles of mouse models for autism spectrum disorders
  • E. Ey, C. Leblond, T. Bourgeron
  • Biology, Psychology
    Autism research : official journal of the International Society for Autism Research
  • 2011
TLDR
Results from therapeutic approaches are encouraging since some behavioral alterations could be reversed even when treatment was performed on adult mice, and ongoing studies should increase the understanding of the biological alterations associated with ASD as well as the development of knowledge‐based treatments.
Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior
TLDR
Evidence for low levels of ultrasonic vocalizations and scent marks in Shank1 −/− mice as compared to wildtype Shank1 +/+ littermate controls is revealed, consistent with a phenotype relevant to social communication deficits in autism.
Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation
TLDR
It is reported that Zn2+ ions, which are highly enriched within the postsynaptic density (PSD), are able to influence the recruitment of ProSAP/Shank proteins to PSDs in a family member‐specific manner during the course of synaptogenesis and synapse maturation.
Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders
TLDR
It is reported that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders.
...
1
2
3
4
5
...