Dendritic spinopathy in transgenic mice expressing ALS/dementia-linked mutant UBQLN2

• DOI: 10.1073/pnas.1405741111
• Publication Date: 2014-09-23T07:21:36Z
• Authors: George H. Gorrie; Faisal Fecto; Daniel Radzicki; Craig Weiss; Yong Shi; Hongxin Dong; Hong Zhai; Ronggen Fu; Erdong Liu; Sisi Li; Hasan Arrat; Eileen H. Bigio; John F. Disterhoft; Marco Martina; Enrico Mugnaini; Teepu Siddique; Han-Xiang Deng
• Keywords: Inclusion Bodies; 0303 health sciences; Microscopy, Confocal; Dendritic Spines; Amyotrophic Lateral Sclerosis; Autophagy-Related Proteins; Brain; Cell Cycle Proteins; Mice, Inbred Strains; Mice, Transgenic; Motor Activity; Hippocampus; Immunohistochemistry; 3. Good health; Disease Models, Animal; Microscopy, Electron; 03 medical and health sciences; Animals; Humans; Dementia; Cognition Disorders; Maze Learning; Adaptor Proteins, Signal Transducing

Significance Mutations in the UBQLN2 gene, which encodes ubiquitin-like protein ubiquilin2 (UBQLN2) have been shown to cause ALS and ALS/dementia. Ubiquilin2 links familial sporadic forms of disease through pathology observed spinal cords all cases brains ALS/dementia with or without mutations. In this communication, we develop characterize a mouse model mutant -linked dementia. We demonstrate that mice impairment degradation pathway, abnormal aggregation, synaptic dysfunction, cognitive deficits. This provides useful tool further study dementia rational therapies.