CYFIP2 p.Arg87Cys Causes Neurological Defects and Degradation of CYFIP2.
basic_science · Level V
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- Record sourced from PubMed, PMID 36251395.
- Also identified by DOI 10.1002/ana.26535.
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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<sup>+/R87C</sup> 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<sup>+/R87C</sup> mice. Beyond identifying a decrease in CYFIP2 protein levels in the Cyfip2<sup>+/R87C</sup> brains, we demonstrated that the p.Arg87Cys variant enhances ubiquitination and proteasomal degradation of CYFIP2. ANN NEUROL 2023;93:155-163.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Spasms, Infantile