G2Cdb::Allele report

Allele Name Type Description Literature
A00000005 H-RAS ko knockout Hras1 (H-ras) knockout  
A00000024 PSD95 GK truncation Dlg4 (PSD-95) guanylate kinase domain deletion  
A00000025 PSD95 ko knockout Dlg4 (PSD-95) knockout  
A00000028 SAP102 ko knockout Dlg3 (SAP102) knockout (17344405)
A00000030 SYNGAP ko knockout Syngap1 (SynGAP) knockout  
  • Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies.

    Cuthbert PC, Stanford LE, Coba MP, Ainge JA, Fink AE, Opazo P, Delgado JY, Komiyama NH, O'Dell TJ and Grant SG

    Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom.

    Understanding the mechanisms whereby information encoded within patterns of action potentials is deciphered by neurons is central to cognitive psychology. The multiprotein complexes formed by NMDA receptors linked to synaptic membrane-associated guanylate kinase (MAGUK) proteins including synapse-associated protein 102 (SAP102) and other associated proteins are instrumental in these processes. Although humans with mutations in SAP102 show mental retardation, the physiological and biochemical mechanisms involved are unknown. Using SAP102 knock-out mice, we found specific impairments in synaptic plasticity induced by selective frequencies of stimulation that also required extracellular signal-regulated kinase signaling. This was paralleled by inflexibility and impairment in spatial learning. Improvement in spatial learning performance occurred with extra training despite continued use of a suboptimal search strategy, and, in a separate nonspatial task, the mutants again deployed a different strategy. Double-mutant analysis of postsynaptic density-95 and SAP102 mutants indicate overlapping and specific functions of the two MAGUKs. These in vivo data support the model that specific MAGUK proteins couple the NMDA receptor to distinct downstream signaling pathways. This provides a mechanism for discriminating patterns of synaptic activity that lead to long-lasting changes in synaptic strength as well as distinct aspects of cognition in the mammalian nervous system.

    Funded by: NIMH NIH HHS: R01 MH060919, R01 MH060919-10; Wellcome Trust: WT077155

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2007;27;10;2673-82

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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