CYFIP2 p.Arg87Cys Causes Neurological Defects and Degradation of CYFIP2

Muwon Kang, Yinhua Zhang, Hyae Rim Kang, Seoyeong Kim, Ruiying Ma, Yunho Yi, Seungjoon Lee, Yoonhee Kim, Huiling Li, Chunmei Jin, Dongmin Lee, Eunjoon Kim, Kihoon Han

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)155-163
Number of pages9
JournalAnnals of Neurology
Volume93
Issue number1
DOIs
Publication statusPublished - 2023 Jan

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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