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Tdp-43 cryptic exons are highly variable between cell types

Jeong, Yun Ha, Ling, Jonathan P., Lin, Sophie Z., Donde, Aneesh N., Braunstein, Kerstin E., Majounie, Elisa, Traynor, Bryan J., LaClair, Katherine D., Lloyd, Thomas E. and Wong, Philip C. 2017. Tdp-43 cryptic exons are highly variable between cell types. Molecular Neurodegeneration 12 10.1186/s13024-016-0144-x

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Background: TDP-43 proteinopathy is a prominent pathological feature that occurs in a number of human diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and inclusion body myositis (IBM). Our recent finding that TDP-43 represses nonconserved cryptic exons led us to ask whether cell type-specific cryptic exons could exist to impact unique molecular pathways in brain or muscle. Methods: In the present work, we investigated TDP-43’s function in various mouse tissues to model disease pathogenesis. We generated mice to conditionally delete TDP-43 in excitatory neurons or skeletal myocytes and identified the cell type-specific cryptic exons associated with TDP-43 loss of function. Results: Comparative analysis of nonconserved cryptic exons in various mouse cell types revealed that only some cryptic exons were common amongst stem cells, neurons, and myocytes; the majority of these nonconserved cryptic exons were cell type-specific. Conclusions: Our results suggest that in human disease, TDP-43 loss of function may impair cell type-specific pathways.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: TDP-43 –Nonconserved cryptic exons, Bioinformatics, Amyotrophic lateral sclerosis, Frontotemporal dementia, Inclusion body myositis
Publisher: BioMed Central
ISSN: 1750-1326
Date of First Compliant Deposit: 22 February 2017
Date of Acceptance: 20 December 2016
Last Modified: 10 Oct 2017 21:13

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