|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Facioscapulohumeral muscular dystrophy (FSHD) has been shown to be related to genetic and epigenetic derepression of DUX4 (mapping to chromosome 4), a gene located within a repeat array of D4Z4 sequences of polymorphic length.
|
30055030 |
2018 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Overall, the FLExDUX4 line of mice is quite versatile and will allow new investigations into mechanisms of DUX4-mediated pathophysiology as well as much-needed pre-clinical testing of DUX4-targeted FSHD interventions in vivo.
|
29415061 |
2018 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
DUX4 plays critical role in the molecular pathogenesis of the neuromuscular disorder facioscapulohumeral muscular dystrophy and acute lymphoblastic leukemia in humans.
|
30322619 |
2018 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
A patient-derived iPSC model revealed oxidative stress increases facioscapulohumeral muscular dystrophy-causative DUX4.
|
30107443 |
2018 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Previous reports showed DUX4-induced gene expression changes as well as changes in microRNA expression in FSHD muscle cells.
|
29741619 |
2018 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
The recent identification of aberrant activation of DUX4 transcription in FSHD as the root cause of FSHD now allows for a targeted approach to therapeutic development.
|
29478599 |
2018 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
We conclude that TIC-DUX4 mice are a relevant model to study DUX4 toxicity and, importantly, are useful in therapeutic development studies for FSHD.
|
30429376 |
2018 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
How DUX4 misexpression contributes to FSHD muscle pathology is a major focus of current investigation.
|
28915324 |
2017 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
The main FSHD form is linked to a reduced copy number of the D4Z4 macrosatellite repeat on 4q35, causing loss of silencing and aberrant expression of the D4Z4-embedded DUX4 gene leading to disease.
|
28040729 |
2017 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
We screened an aggregated chemical library enriched for compounds with epigenetic activities and the Pharmakon 1600 library composed of compounds that have reached clinical testing to identify molecules that decrease DUX4 expression as monitored by the levels of DUX4 target genes in FSHD patient-derived skeletal muscle cell cultures.
|
28870238 |
2017 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Our findings are consistent with the hypothesis that muscle damage in FSHD is due to DUX4-mediated toxicity causing destruction of terminally differentiated myofibers.
|
28637492 |
2017 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
We found robust expression of DUX4-fl in most FSHD LCLs and a good correlation between DNA hypomethylation and repeat length.
|
28161093 |
2017 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Estrogen effects are mediated by estrogen receptor β (ERβ), which reduces chromatin occupancy and transcriptional activity of double homeobox 4 (DUX4), a protein whose aberrant expression has been implicated in FSHD pathogenesis.
|
28263188 |
2017 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Facioscapulohumeral muscular dystrophy (FSHD) is caused by inappropriate expression of the double homeodomain protein DUX4.
|
28935672 |
2017 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Here, we show that suppression of PAX7 target genes is a hallmark of FSHD, and that it is as major a signature of FSHD muscle as DUX4 target gene expression.
|
29255294 |
2017 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
This mouse model will facilitate in vivo testing of therapeutics, and suggests the involvement of fibroadipogenic progenitors in facioscapulohumeral muscular dystrophy.Facioscapulohumeral muscular dystrophy is a severe myopathy that is caused by abnormal activation of DUX4, and for which a suitable mouse model does not exist.
|
28916757 |
2017 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Aberrant expression of the D4Z4 ORF called DUX4 is associated with the pathogenesis of Facioscapulohumeral muscular dystrophy (FSHD).
|
28173143 |
2016 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
FSHD is associated with partial chromatin relaxation of the D4Z4 repeat array on chromosome 4 and the somatic expression of the D4Z4 encoded DUX4 gene.
|
25782668 |
2016 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Electroporation of FM10 into FSHD patient muscle xenografts in mice also down-regulated DUX4 and DUX4 targets.
|
27378237 |
2016 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
A unifying pathogenic model for FSHD emerged with the recognition that the FSHD-permissive 4qA haplotype corresponds to a polyadenylation signal that stabilizes the DUX4 mRNA, allowing the toxic protein DUX4 to be expressed.
|
27816329 |
2016 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Double homeobox 4 (DUX4), the major actor in FSHD pathology induced DNA damage accumulation when overexpressed in normal human myoblasts, and RNAi-mediated DUX4 inhibition reduced the level of DNA damage in FSHD myoblasts.
|
27519269 |
2016 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
These results implicate the promoter and exon 1 of DUX4 as potential therapeutic targets and demonstrate the utility of CRISPR technology for correction of the epigenetic dysregulation in FSHD.
|
26527377 |
2016 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
The endogenous expression of DUX4-fl in FSHD-derived human muscle and myogenic cells is extremely low, exogenous expression of DUX4-fl in somatic cells rapidly induces cytotoxicity, and, due in part to the lack of conservation beyond primate lineages, viable animal models based on DUX4-fl have been difficult to generate.
|
26942723 |
2016 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Double homeobox 4 (DUX4) gene, encoded within each D4Z4 unit, is normally transcriptionally silenced but is found aberrantly expressed in skeletal muscles of FSHD patients.
|
26860865 |
2016 |
|
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
PosttranslationalModification
|
disease |
BEFREE |
Loss of epigenetic silencing of the DUX4 transcription factor gene in facioscapulohumeral muscular dystrophy.
|
26113644 |
2015 |