Activity-dependent FUS dysregulation disrupts synaptic homeostasis

• DOI: 10.1073/pnas.1406162111
• Publication Date: 2014-10-17T12:20:08Z
• Authors: Chantelle F. Sephton; Amy A. Tang; Ashwinikumar Kulk...; James West; Mieu Brooks; Jeremy J. Stubble...; Yun Liu; Michael Q. Zhang; Carla B. Green; Kimberly M. Huber; Eric J. Huang; Joachim Herz; Gang Yu
• Keywords: Wild type; Frontotemporal lobar degeneration; Loss function

Significance Both overexpression of wild-type fused in sarcoma (FUS) protein and missense mutations can be pathogenic a group related neurodegenerative disorders that includes amyotrophic lateral sclerosis frontotemporal lobar degeneration. It is unclear how FUS cause disease human patients. In this work, we generated novel transgenic mouse models expressing low levels mutant FUS, both which recapitulate aspects the diseases. We found profound difference underlying mechanisms by mutation disease. Overexpression alters its nuclear function at level gene expression. contrast, disrupts activity-dependent synaptic homeostasis to gain toxic dendritic spines.