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Altered thalamocortical development in the SAP102 knockout model of intellectual disability.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2016 Sep 15; Vol. 25 (18), pp. 4052-4061. Date of Electronic Publication: 2016 Jul 27. - Publication Year :
- 2016
-
Abstract
- Genetic mutations known to cause intellectual disabilities (IDs) are concentrated in specific sets of genes including both those encoding synaptic proteins and those expressed during early development. We have characterized the effect of genetic deletion of Dlg3, an ID-related gene encoding the synaptic NMDA-receptor interacting protein synapse-associated protein 102 (SAP102), on development of the mouse somatosensory cortex. SAP102 is the main representative of the PSD-95 family of postsynaptic MAGUK proteins during early development and is proposed to play a role in stabilizing receptors at immature synapses. Genetic deletion of SAP102 caused a reduction in the total number of thalamocortical (TC) axons innervating the somatosensory cortex, but did not affect the segregation of barrels. On a synaptic level SAP102 knockout mice display a transient speeding of NMDA receptor kinetics during the critical period for TC plasticity, despite no reduction in GluN2B-mediated component of synaptic transmission. These data indicated an interesting dissociation between receptor kinetics and NMDA subunit expression. Following the critical period NMDA receptor function was unaffected by loss of SAP102 but there was a reduction in the divergence of TC connectivity. These data suggest that changes in synaptic function early in development caused by mutations in SAP102 result in changes in network connectivity later in life.<br /> (© The Author 2016. Published by Oxford University Press.)
- Subjects :
- Animals
Humans
Intellectual Disability physiopathology
Mice
Mice, Knockout
Receptors, N-Methyl-D-Aspartate genetics
Sequence Deletion
Somatosensory Cortex pathology
Synaptic Transmission genetics
Embryonic Development genetics
Guanylate Kinases genetics
Intellectual Disability genetics
Membrane Proteins genetics
Somatosensory Cortex growth & development
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 25
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 27466188
- Full Text :
- https://doi.org/10.1093/hmg/ddw244