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rs80356733
|
|
|
0.070 |
GeneticVariation |
BEFREE |
To investigate spinal cord synaptic dysfunction, we took advantage of a zebrafish larval model and expressed either wild type human TARDBP (wtTARDBP) or the ALS-causing G348C variant (mutTARDBP).
|
31235725 |
2019 |
|
rs80356733
|
|
|
0.070 |
GeneticVariation |
BEFREE |
We have generated Caenorhabditis elegans and zebrafish animal models expressing mutant human TDP-43 (A315T or G348C) or FUS (S57Δ or R521H) that reflect certain aspects of ALS including motor neuron degeneration, axonal deficits, and progressive paralysis.
|
22848727 |
2012 |
|
rs80356733
|
|
|
0.070 |
GeneticVariation |
BEFREE |
Here we expressed the wild-type human gene (wtTARDBP) or the ALS mutation G348C (mutTARDBP) in zebrafish larvae and characterized their motor (swimming) activity and the structure and function of their neuromuscular junctions (NMJs).
|
23345247 |
2013 |
|
rs80356733
|
|
|
0.070 |
GeneticVariation |
BEFREE |
We generated transgenic zebrafish lines expressing human TDP-43, either the wild-type form or the ALS-causative G348C mutation identified in a subset of ALS patients, with the transgene expression driven by an inducible heat shock promoter in order to bypass a potential early mortality.
|
30618614 |
2018 |
|
rs80356733
|
|
|
0.070 |
GeneticVariation |
BEFREE |
We previously developed a mouse model of ALS that exhibits adult-onset motor dysfunction; these mutant TDP-43 knock in (KI) mice heterozygously express mutant human TDP-43 (A382T or G348C).
|
26672899 |
2016 |
|
rs80356730
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Ectopic expression of ALS-associated mutant human TDP-43 (hTDP-43(M337V) and hTDP-43(Q331K)) produces a less severe SOP phenotype than hTDP-43(WT), indicating a partial loss of function of mutant hTDP-43.
|
23042786 |
2013 |
|
rs80356730
|
|
|
0.060 |
GeneticVariation |
BEFREE |
We then investigated the effects of one of these allele-specific siRNAs in induced pluripotent stem cells (iPSCs) derived from an ALS patient carrying the M337V mutation.
|
24651281 |
2014 |
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rs80356730
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Taken together, our results confirmed that TDP-43-M337V impaired the Nrf2/ARE pathway by reducing the expression of MafK and JDP2 proteins, and provided information for further research on the molecular mechanisms of TDP-43-M337V in ALS.
|
28510254 |
2017 |
|
rs80356730
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Here, as facilitated by our previous discovery, by circular dichroism (CD), fluorescence and nuclear magnetic resonance (NMR) spectroscopy, we have successfully determined conformations, dynamics, and self-associations of the full-length prion-like domains of the wild type and three ALS-causing mutants (A315E, Q331K, and M337V) in both aqueous solutions and membrane environments.
|
26735904 |
2016 |
|
rs80356730
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Overexpression of ALS-associated p.M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice.
|
23475610 |
2013 |
|
rs80356730
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Single-copy expression of an amyotrophic lateral sclerosis-linked TDP-43 mutation (M337V) in BAC transgenic mice leads to altered stress granule dynamics and progressive motor dysfunction.
|
30290270 |
2019 |
|
rs80356715
|
|
|
0.040 |
GeneticVariation |
BEFREE |
We generated multiple iPSC lines from an FTD/ALS patient with the TARDBP A90V mutation and from an unaffected family member who lacked the mutation.
|
24143176 |
2013 |
|
rs80356715
|
|
|
0.040 |
GeneticVariation |
BEFREE |
Thus, A90V may be a genetic risk factor for FTLD/ALS because it predisposes nuclear TDP-43 to redistribute to the cytoplasm and form pathological aggregates.
|
18505686 |
2008 |
|
rs80356715
|
|
|
0.040 |
GeneticVariation |
BEFREE |
The p.A90V and p.G357R variations were detected in the same patient and p.R361T was present in a family with both ALS and frontotemporal dementia-ALS.
|
22456481 |
2012 |
|
rs80356715
|
|
|
0.040 |
GeneticVariation |
BEFREE |
We conclude that in the absence of another genetic or environmental 'hit' the A90V variant is not sufficient to cause the deleterious phenotypes associated with ALS and FTD, despite prominent cytoplasmic protein relocalization of TDP-43.
|
28286471 |
2017 |
|
rs80356727
|
|
|
0.040 |
GeneticVariation |
BEFREE |
Amyotrophic lateral sclerosis-associated TDP-43 mutation Q331K prevents nuclear translocation of XRCC4-DNA ligase 4 complex and is linked to genome damage-mediated neuronal apoptosis.
|
31067307 |
2019 |
|
rs80356727
|
|
|
0.040 |
GeneticVariation |
BEFREE |
The contribution of mutant TDP-43-mediated damage within motor neurons was evaluated using mice expressing a conditional allele of an ALS-causing TDP-43 mutant (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43.
|
28357566 |
2017 |
|
rs80356727
|
|
|
0.040 |
GeneticVariation |
BEFREE |
The transactivating response region DNA binding protein 43 (TDP-43) p.Q331K mutation (TDP-43 Q331K) has previously been identified in ALS as a disease-causing mutation with neurotoxicity.
|
30376609 |
2019 |
|
rs80356727
|
|
|
0.040 |
GeneticVariation |
BEFREE |
Ectopic expression of ALS-associated mutant human TDP-43 (hTDP-43(M337V) and hTDP-43(Q331K)) produces a less severe SOP phenotype than hTDP-43(WT), indicating a partial loss of function of mutant hTDP-43.
|
23042786 |
2013 |
|
rs4884357
|
|
|
0.020 |
GeneticVariation |
BEFREE |
Systematically analysing ALS-related TDP-43 mutants (G298S, M337V, and Q331K) in different buffer conditions at different temperatures, we prove that this phase separation is driven by hydrophobic interactions but is inhibited by electrostatic repulsion.
|
28988034 |
2018 |
|
rs4884357
|
|
|
0.020 |
GeneticVariation |
BEFREE |
In this study, using iPSCs-derived human MN from an ALS patient with a TDP43 G298S mutation and two sporadic ALS patients, we showed that both sporadic and familial ALS were characterized by TDP-43 aggregates in the surviving MN.
|
30442180 |
2018 |
|
rs766196255
|
|
|
0.020 |
GeneticVariation |
BEFREE |
We identified a novel mutation, c.1069G > A (p.Gly357Ser) and a known mutation in sporadic ALS.
|
20675015 |
2012 |
|
rs766196255
|
|
|
0.020 |
GeneticVariation |
BEFREE |
Dysregulation of TDP-43 intracellular localization and early onset ALS are associated with a TARDBP S375G variant.
|
30461104 |
2019 |
|
rs80356717
|
|
|
0.020 |
GeneticVariation |
BEFREE |
One of the multitasking proteins, transactive response DNA-binding protein 43 (tdp43) plays a key role in RNA regulation and the two pathogenic mutations such as D169G and K263E, located at the RNA Recognition Motif (RRM) of tdp43, are reported to cause neurological disorders such as Amyotrophic Lateral Sclerosis and FrontoTemporal Lobar Degeneration.
|
28330421 |
2018 |
|
rs80356717
|
|
|
0.020 |
GeneticVariation |
BEFREE |
Although ALS-causing TARDBP mutations cluster in the C-terminal glycine-rich region of the protein, the pathogenic nature of the atypical missense variants p.A90V (located between the bipartite nuclear localization signal) and p.D169G (located in the first RNA-binding domain) is unclear.
|
25442115 |
2015 |