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

Zhou, H and Huang, C and Chen, H and Wang, D and Landel, CP and Xia, PY and Bowser, R and Liu, YJ and Xia, XG (2010) Transgenic rat model of neurodegeneration caused by mutation in the TDP gene. PLoS Genetics, 6 (3). ISSN 1553-7390

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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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Zhou, H
Huang, C
Chen, H
Wang, D
Landel, CP
Xia, PY
Bowser, R
Liu, YJ
Xia, XG
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 March 2010
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 6
Number: 3
DOI or Unique Handle: 10.1371/journal.pgen.1000887
Refereed: Yes
ISSN: 1553-7390
MeSH Headings: Amyotrophic Lateral Sclerosis--genetics; Amyotrophic Lateral Sclerosis--metabolism; Amyotrophic Lateral Sclerosis--pathology; Animals; DNA-Binding Proteins--genetics; DNA-Binding Proteins--metabolism; Disease Models, Animal; Female; Humans; Male; Mutation; Rats; Rats, Sprague-Dawley; Rats, Transgenic
Other ID: NLM PMC2845661
PubMed Central ID: PMC2845661
PubMed ID: 20361056
Date Deposited: 03 Aug 2012 18:56
Last Modified: 02 Feb 2019 16:56


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