Mutations that cause intellectual disability (ID) and autism spectrum disorder (ASD) are commonly found in genes that encode for synaptic proteins. Syngap1 [synaptic Ras GTPase activating protein 1 homolog (rat)] encodes a synaptic RasGAP (SynGAP) that is largely localized to dendritic spines in neocortical pyramidal neurons, where it suppresses signaling pathways linked to NMDA receptor (NMDAR)-mediated synaptic plasticity and AMPA receptor (AMPAR) membrane insertion. Syngap1 has alternative transcriptional start sites and several alternatively spliced C-terminal exons that result in many possible SynGAP isoforms. Human SYNGAP1 haploinsufficiency results from a truncation of the full-length protein. Humanized SYNGAP1hu knock-in/knock-out mice have a BAC expressing human SYNGAP1 and ZBTB9 that replace the coding region of the mouse Syngap1 and most of Zbtb9 locus. Mice homozygous for the mutation are viable and fertile with no obvious phentoype. RT-qPCR analysis from the mouse cortex indicates that these mice express no detectable mouse Syngap1, but do express an equivalent level of human SYNGAP1.

Humanized SYNGAP1hu knock-in/knock-out mice express human SYNGAP1. RT-qPCR analysis from the mouse cortex indicates that these mice express no detectable mouse Syngap1, but do express an equivalent level of human SYNGAP1. This strain may be useful for studies of intellectual disability (ID) and autism spectrum disorder (ASD).

This strain is hosted by NIH's MMRRC, which partners with JAX for the distribution of this and other strains. For additional information and to purchase, please visit the MMRRC site.