CYFIP2 p.Arg87Cys Causes Neurological Defects and Degradation of CYFIP2.
Ann Neurol
; 93(1): 155-163, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36251395
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;93155-163.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espasmos Infantis
/
Proteínas Adaptadoras de Transdução de Sinal
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article