FUS transgenic rats develop the phenotypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

Authors

Cao Huang, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Hongxia Zhou, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Jianbin Tong, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Han Chen, Center for Biotechnology, University of Nebraska–Lincoln, Lincoln, NebraskaFollow
Yong-Jian Liu, Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PennsylvaniaFollow
Dian Wang, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Xiaotao Wei, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Xu-Gang Xia, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow

Document Type

Article

Publication Date

3-1-2011

Comments

This article has been peer reviewed and is published in PLoS Genetics 2011, 7(3). The published version is available at DOI: 10.1371/journal.pgen.1002011. © Public Library of Science

Abstract

Fused in Sarcoma (FUS) proteinopathy is a feature of frontotemporal lobar dementia (FTLD), and mutation of the fus gene segregates with FTLD and amyotrophic lateral sclerosis (ALS). To study the consequences of mutation in the fus gene, we created transgenic rats expressing the human fus gene with or without mutation. Overexpression of a mutant (R521C substitution), but not normal, human FUS induced progressive paralysis resembling ALS. Mutant FUS transgenic rats developed progressive paralysis secondary to degeneration of motor axons and displayed a substantial loss of neurons in the cortex and hippocampus. This neuronal loss was accompanied by ubiquitin aggregation and glial reaction. While transgenic rats that overexpressed the wild-type human FUS were asymptomatic at young ages, they showed a deficit in spatial learning and memory and a significant loss of cortical and hippocampal neurons at advanced ages. These results suggest that mutant FUS is more toxic to neurons than normal FUS and that increased expression of normal FUS is sufficient to induce neuron death. Our FUS transgenic rats reproduced some phenotypes of ALS and FTLD and will provide a useful model for mechanistic studies of FUS-related diseases.

Recommended Citation

Huang, Cao; Zhou, Hongxia; Tong, Jianbin; Chen, Han; Liu, Yong-Jian; Wang, Dian; Wei, Xiaotao; and Xia, Xu-Gang, "FUS transgenic rats develop the phenotypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration." (2011). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 66.
https://jdc.jefferson.edu/pacbfp/66

PubMed ID

21408206