Title

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

Document Type

Article

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. © 2010 Zhou et al.

Publication Date

3-1-2010

Publication Title

PLoS Genetics

ISSN

15537390

E-ISSN

15537404

Volume

6

Issue

3

PubMed ID

20361056

Digital Object Identifier (DOI)

10.1371/journal.pgen.1000887

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