Here, we report the generation and comprehensive characterization of a knockin mouse model for the hotspot p.Arg87Cys variant of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) gene, which was recently identified in individuals diagnosed with West syndrome, a developmental and epileptic encephalopathy. The Cyfip2+/R87C mice recapitulated many neurological and neurobehavioral phenotypes of the patients, including spasmlike movements, microcephaly, and impaired social communication. Age-progressive cytoarchitectural disorganization and gliosis were also identified in the hippocampus of Cyfip2+/R87C mice. Beyond identifying a decrease in CYFIP2 protein levels in the Cyfip2+/R87C brains, we demonstrated that the p.Arg87Cys variant enhances ubiquitination and proteasomal degradation of CYFIP2. ANN NEUROL 2023;93:155–163.
Bibliographical noteFunding Information:
This study was supported by National Research Foundation of Korea (NRF) grants funded by the Korea Government Ministry of Science and Information and Communications Technology (NRF‐2018M3C7A1024603 and NRF‐2021R1A2C4001429 to K.H.), by the Institute for Basic Science (IBS‐R002‐D1 to E.K.), and by a Korea University grant (K2118761 to K.H.).
© 2022 American Neurological Association.
ASJC Scopus subject areas
- Clinical Neurology