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
|
Preview |
PDF
- Published Version
Download (3MB) | Preview |
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: | Schools > Medicine Research Institutes & Centres > 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: | 15 May 2023 10:51 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/98472 |
Citation Data
Cited 43 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
 |
Edit Item |
Dimensions
Dimensions