Tdp-43 cryptic exons are highly variable between cell types

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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article number13
JournalMolecular Neurodegeneration
Volume12
Issue number1
DOIs
StatePublished - Feb 2 2017

Fingerprint

Exons
TDP-43 Proteinopathies
Inclusion Body Myositis
Neurons
Skeletal Muscle Fibers
Muscle Cells
Stem Cells
Muscles
Brain

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

Cite this

Jeong, Y. H., Ling, J. P., Lin, S. Z., Donde, A. N., Braunstein, K. E., Majounie, E., ... Wong, P. C. (2017). Tdp-43 cryptic exons are highly variable between cell types. Molecular Neurodegeneration, 12(1), [13]. https://doi.org/10.1186/s13024-016-0144-x

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; Traynor, Bryan J.; LaClair, Katherine D.; Lloyd, Thomas; Wong, Philip Chun.

In: Molecular Neurodegeneration, Vol. 12, No. 1, 13, 02.02.2017.

Research output: Contribution to journalArticle

Jeong, YH, Ling, JP, Lin, SZ, Donde, AN, Braunstein, KE, Majounie, E, Traynor, BJ, LaClair, KD, Lloyd, T & Wong, PC 2017, 'Tdp-43 cryptic exons are highly variable between cell types', Molecular Neurodegeneration, vol. 12, no. 1, 13. https://doi.org/10.1186/s13024-016-0144-x
Jeong YH, Ling JP, Lin SZ, Donde AN, Braunstein KE, Majounie E et al. Tdp-43 cryptic exons are highly variable between cell types. Molecular Neurodegeneration. 2017 Feb 2;12(1). 13. https://doi.org/10.1186/s13024-016-0144-x
Jeong, Yun Ha ; Ling, Jonathan P. ; Lin, Sophie Z. ; Donde, Aneesh N. ; Braunstein, Kerstin E. ; Majounie, Elisa ; Traynor, Bryan J. ; LaClair, Katherine D. ; Lloyd, Thomas ; Wong, Philip Chun. / Tdp-43 cryptic exons are highly variable between cell types. In: Molecular Neurodegeneration. 2017 ; Vol. 12, No. 1.
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