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.
Original language | English (US) |
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Article number | 13 |
Journal | Molecular neurodegeneration |
Volume | 12 |
Issue number | 1 |
DOIs | |
State | Published - Feb 2 2017 |
Keywords
- Amyotrophic lateral sclerosis
- Bioinformatics
- Frontotemporal dementia
- Inclusion body myositis
- TDP-43 -Nonconserved cryptic exons
ASJC Scopus subject areas
- Molecular Biology
- Clinical Neurology
- Cellular and Molecular Neuroscience