Tdp-43 cryptic exons are highly variable between cell types. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Jeong, Yun; Ling, Jonathan; Lin, Sophie; Donde, Aneesh; Braunstein, Kerstin; Majounie, Elisa; Traynor, Bryan; LaClair, Katherine; Lloyd, Thomas; Wong, Philip
• Is Part Of: Molecular neurodegeneration. Volume 12:Issue 1(2017)
• Page Start: 1
• Page End: 9
• Publication Date: 2017-12
• Subjects: TDP-43 –Nonconserved cryptic exons -- Bioinformatics -- Amyotrophic lateral sclerosis -- Frontotemporal dementia -- Inclusion body myositis; Neurobiology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1186/s13024-016-0144-x
• Languages: English
• ISSNs: 1750-1326

Abstract

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.