CYFIP2 p.Arg87Cys Causes Neurological Defects and Degradation of CYFIP2.
Muwon KangYinhua ZhangHyae Rim KangSeoyeong KimRuiying MaYunho YiSeungjoon LeeYoonhee KimHuiling LiChunmei JinDongmin LeeEunjoon KimKihoon HanPublished in: Annals of neurology (2022)
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 2022.
Keyphrases
- mouse model
- end stage renal disease
- multiple sclerosis
- newly diagnosed
- zika virus
- chronic kidney disease
- ejection fraction
- early onset
- mental health
- type diabetes
- high fat diet induced
- small molecule
- gene expression
- genome wide
- protein protein
- amino acid
- intellectual disability
- skeletal muscle
- binding protein
- adipose tissue
- peritoneal dialysis
- patient reported outcomes
- protein kinase
- wild type