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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 ORCID: https://orcid.org/0000-0003-2800-1091, 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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Abstract

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: 02 Nov 2022 10:23
URI: https://orca.cardiff.ac.uk/id/eprint/98472

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