A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency

Elife. 2020 Jan 15:9:e52656. doi: 10.7554/eLife.52656.


SynGAP is a postsynaptic density (PSD) protein that binds to PDZ domains of the scaffold protein PSD-95. We previously reported that heterozygous deletion of Syngap1 in mice is correlated with increased steady-state levels of other key PSD proteins that bind PSD-95, although the level of PSD-95 remains constant (Walkup et al., 2016). For example, the ratio to PSD-95 of Transmembrane AMPA-Receptor-associated Proteins (TARPs), which mediate binding of AMPA-type glutamate receptors to PSD-95, was increased in young Syngap1+/-mice. Here we show that only females and not males show a highly significant correlation between an increase in TARP and a decrease in synGAP in the PSDs of Syngap1+/-rodents. The data reveal a sex difference in the adaptation of the PSD scaffold to synGAP haploinsufficiency.

Keywords: biochemistry; chemical biology; glutamate receptor; mouse; neuroscience; rat; synGAP; synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • CRISPR-Cas Systems
  • Female
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Haploinsufficiency*
  • Male
  • Mice
  • Mice, Knockout
  • Phosphorylation
  • Post-Synaptic Density / metabolism*
  • Sex Factors


  • GTPase-Activating Proteins
  • Syngap1 protein, rat