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) |
|---|---|
| Article number | 13 |
| Journal | Molecular Neurodegeneration |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 2 2017 |
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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
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 journal › Article
}
TY - JOUR
T1 - Tdp-43 cryptic exons are highly variable between cell types
AU - Jeong, Yun Ha
AU - Ling, Jonathan P.
AU - Lin, Sophie Z.
AU - Donde, Aneesh N.
AU - Braunstein, Kerstin E.
AU - Majounie, Elisa
AU - Traynor, Bryan J.
AU - LaClair, Katherine D.
AU - Lloyd, Thomas
AU - Wong, Philip Chun
PY - 2017/2/2
Y1 - 2017/2/2
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - Bioinformatics
KW - Frontotemporal dementia
KW - Inclusion body myositis
KW - TDP-43 -Nonconserved cryptic exons
UR - http://www.scopus.com/inward/record.url?scp=85011304395&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011304395&partnerID=8YFLogxK
U2 - 10.1186/s13024-016-0144-x
DO - 10.1186/s13024-016-0144-x
M3 - Article
C2 - 28153034
AN - SCOPUS:85011304395
VL - 12
JO - Molecular Neurodegeneration
JF - Molecular Neurodegeneration
SN - 1750-1326
IS - 1
M1 - 13
ER -