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Open Access 01-12-2017 | Research article

Tdp-43 cryptic exons are highly variable between cell types

Authors: Yun Ha Jeong, Jonathan P. Ling, Sophie Z. Lin, Aneesh N. Donde, Kerstin E. Braunstein, Elisa Majounie, Bryan J. Traynor, Katherine D. LaClair, Thomas E. Lloyd, Philip C. Wong

Published in: Molecular Neurodegeneration | Issue 1/2017

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.

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Title: Tdp-43 cryptic exons are highly variable between cell types
Authors: Yun Ha Jeong
Jonathan P. Ling
Sophie Z. Lin
Aneesh N. Donde
Kerstin E. Braunstein
Elisa Majounie
Bryan J. Traynor
Katherine D. LaClair
Thomas E. Lloyd
Philip C. Wong
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2017
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/s13024-016-0144-x

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Tdp-43 cryptic exons are highly variable between cell types

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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