[HTML][HTML] Tdp-43 cryptic exons are highly variable between cell types
YH Jeong, JP Ling, SZ Lin, AN Donde… - Molecular …, 2017 - Springer
Molecular neurodegeneration, 2017•Springer
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 …
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 …
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.
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