Transgenic rat model of neurodegeneration caused by mutation in the TDP gene.

Authors

Hongxia Zhou, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PAFollow
Cao Huang, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PAFollow
Han Chen, Center for Biotechnology, University of Nebraska–Lincoln, Lincoln, NEFollow
Dian Wang, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PAFollow
Carlisle P Landel, Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PAFollow
Pedro Yuxing Xia, Lower Merion High School, Ardmore, PAFollow
Robert Bowser, Department of Pathology, Center of ALS Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA
Yong-Jian Liu, Department of Neurobiology, School of Medicine, University of Pittsburgh, PAFollow
Xu Gang Xia, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PAFollow

Document Type

Article

Publication Date

3-1-2010

Comments

This article has been peer reviewed and is published in PLoS Genetics 2010, 6(3). The published version is available at DOI: 10.1371/journal.pgen.1000887. © Public Library of Science

Abstract

TDP-43 proteinopathies have been observed in a wide range of neurodegenerative diseases. Mutations in the gene encoding TDP-43 (i.e., TDP) have been identified in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobe degeneration associated with motor neuron disease. To study the consequences of TDP mutation in an intact system, we created transgenic rats expressing normal human TDP or a mutant form of human TDP with a M337V substitution. Overexpression of mutant, but not normal, TDP caused widespread neurodegeneration that predominantly affected the motor system. TDP mutation reproduced ALS phenotypes in transgenic rats, as seen by progressive degeneration of motor neurons and denervation atrophy of skeletal muscles. This robust rat model also recapitulated features of TDP-43 proteinopathies including the formation of TDP-43 inclusions, cytoplasmic localization of phosphorylated TDP-43, and fragmentation of TDP-43 protein. TDP transgenic rats will be useful for deciphering the mechanisms underlying TDP-43-related neurodegenerative diseases.

Recommended Citation

Zhou, Hongxia; Huang, Cao; Chen, Han; Wang, Dian; Landel, Carlisle P; Xia, Pedro Yuxing; Bowser, Robert; Liu, Yong-Jian; and Xia, Xu Gang, "Transgenic rat model of neurodegeneration caused by mutation in the TDP gene." (2010). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 67.
https://jdc.jefferson.edu/pacbfp/67

PubMed ID

20361056