INT255131

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Context Info
Confidence 0.77
First Reported 2008
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 34
Total Number 36
Disease Relevance 10.44
Pain Relevance 0.55

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

mRNA processing (Mbnl1) RNA binding (Mbnl1) nucleus (Mbnl1)
cytoplasm (Mbnl1)
Anatomy Link Frequency
skeletal muscle 3
nucleus 2
myoblast 2
neurons 2
muscle 1
Mbnl1 (Mus musculus)
Pain Link Frequency Relevance Heat
gABA 144 99.08 Very High Very High Very High
GABAergic 160 95.84 Very High Very High Very High
imagery 172 94.08 High High
interneuron 16 49.36 Quite Low
anticonvulsant 3 43.76 Quite Low
Pain 3 42.16 Quite Low
Kinase C 9 26.08 Quite Low
medulla 16 21.76 Low Low
anesthesia 40 5.00 Very Low Very Low Very Low
tolerance 39 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Targeted Disruption 616 99.84 Very High Very High Very High
Frailty 425 99.64 Very High Very High Very High
Disease 292 98.84 Very High Very High Very High
Hypopituitarism 107 96.36 Very High Very High Very High
Neurodegenerative Disease 32 96.04 Very High Very High Very High
Congenital Anomalies 133 94.28 High High
Starvation 9 88.84 High High
Arrhythmia Under Development 31 84.60 Quite High
Myotonia 28 83.56 Quite High
Cataract 44 79.64 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In contrast, SCA8 and DM1 Purkinje cells have clearly detectable nuclear CUG foci but these foci do not co-localize with MBNL1, which is predominantly expressed in the cytoplasm (Figure 1B, middle and bottom row arrows).
Gene_expression (expressed) of MBNL1 in Purkinje cells
1) Confidence 0.77 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.14 Pain Relevance 0
These data also suggest that MBNL1 overexpression, which has been demonstrated to be therapeutic in skeletal muscle, might also be an effective treatment to reverse pathological changes associated with expression of CUGexp transcripts in the CNS.
Gene_expression (overexpression) of MBNL1 in skeletal muscle
2) Confidence 0.77 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.25 Pain Relevance 0.07
Previous studies in myotonic dystrophy suggest that the expression of CUGexp transcripts, together with MBNL1 and CELF proteins and their downstream target genes need to be coordinated temporally and spatially for disease pathogenesis.
Gene_expression (expression) of MBNL1 associated with frailty and disease
3) Confidence 0.77 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.37 Pain Relevance 0.03
Third, we demonstrate SCA8 CUGexp transcripts trigger increased expression of a CUGBP1-MBNL1 regulated CNS target, GABT4, in both mice and humans as well as in a human cell culture model and demonstrate the predicted loss of GABAergic inhibition within the granular cell layer occurs in these animals.
Gene_expression (expression) of CUGBP1-MBNL1 associated with gabaergic
4) Confidence 0.77 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.08 Pain Relevance 0.05
Here, we present three lines of evidence that RNA gain-of-function plays a significant role in SCA8: 1) CUGexp transcripts accumulate as ribonuclear inclusions that co-localize with MBNL1 in selected neurons in the brain; 2) loss of Mbnl1 enhances motor deficits in SCA8 mice; 3) SCA8 CUGexp transcripts trigger splicing changes and increased expression of the CUGBP1-MBNL1 regulated CNS target, GABA-A transporter 4 (GAT4/Gabt4).
Gene_expression (expression) of CUGBP1-MBNL1 in brain associated with gaba
5) Confidence 0.77 Published 2009 Journal PLoS Genetics Section Abstract Doc Link PMC2719092 Disease Relevance 0.22 Pain Relevance 0.14
Consistent with our results, over expression of MBNL1 in transgenic mice expressing CTG tracts allows the rescue of both the splice defects and myotonia [50].
Gene_expression (expression) of MBNL1 associated with targeted disruption and hypopituitarism
6) Confidence 0.73 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.36 Pain Relevance 0
We have shown that re-expression of MBNL1 is sufficient to rescue the IR splice defects in DM1 patient cells [46], [47].
Gene_expression (expression) of MBNL1
7) Confidence 0.73 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.34 Pain Relevance 0
The importance of MBNL1 function for maintenance of adult splicing patterns is highlighted by the fact that viral overexpression of Mbnl1 in skeletal muscle of a CUGexp mouse model promotes adult splicing patterns for Clcn1, Tnnt3 and Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 1 (Serca1) [17].
Gene_expression (overexpression) of Mbnl1 in skeletal muscle
8) Confidence 0.67 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2874217 Disease Relevance 0.36 Pain Relevance 0
Although heterozygous Mbnl1+/?
Gene_expression (/) of Mbnl1
9) Confidence 0.67 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.59 Pain Relevance 0
In support of the model that SCA8 CUGexp transcripts affect MBNL1 regulated pathways, expression of human SCA8 cDNA transcripts (ATXN8OS) in Drosophila photoreceptor neurons induce a late-onset, neurodegenerative phenotype genetically enhanced by the loss of the fly MBNL1 orthologue muscleblind [24].
Gene_expression (expression) of MBNL1 in neurons associated with neurodegenerative disease
10) Confidence 0.67 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.72 Pain Relevance 0
 ; Mbnl1+/?
Gene_expression (/) of Mbnl1
11) Confidence 0.67 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.49 Pain Relevance 0
We show that overexpression of CUGBP1 in human SK-N-SH cells, or depletion of MBNL1, result in an upregulation of GABT4 that mimics the in vivo changes in steady state levels caused by CUGexp transcripts.
Gene_expression (overexpression) of MBNL1 in SK-N-SH
12) Confidence 0.67 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.08 Pain Relevance 0.08
Similar to humans, Gabt4 is also up-regulated in the SCA8 BAC-Exp and Mbnl1?
Gene_expression (is) of Mbnl1
13) Confidence 0.67 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.08 Pain Relevance 0
Evidence that MBNL1 loss-of-function plays a role in DM was suggested by studies showing MBNL1 co-localizes with CUG or CCUG ribonuclear inclusions [10] with additional strong support coming from Mbnl1 isoform knockout mice (Mbnl1?
Gene_expression (loss) of MBNL1 associated with targeted disruption and frailty
14) Confidence 0.67 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 1.08 Pain Relevance 0
In these experiments no significant alteration in steady-state Mbnl1 levels were detected in ?
Gene_expression (levels) of Mbnl1
15) Confidence 0.63 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0 Pain Relevance 0
Consistent with our results, over expression of MBNL1 in transgenic mice expressing CTG tracts allows the rescue of both the splice defects and myotonia [50].
Gene_expression (expression) of MBNL1 associated with targeted disruption and hypopituitarism
16) Confidence 0.63 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.36 Pain Relevance 0
Nonetheless, MBNL1 inactivation must be a key event in DM1 myoblasts as over expression of MBNL1 is sufficient to rescue the splice defects in these cells [46], [47].
Gene_expression (expression) of MBNL1 in myoblasts
17) Confidence 0.63 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0 Pain Relevance 0
Similar, but relatively small amounts of endogenous MBNL1, localize both in nuclear CUG foci (?
Gene_expression (amounts) of MBNL1
18) Confidence 0.63 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.18 Pain Relevance 0
As previous studies have shown marked sequestration of MBNL1 in CUG foci both in skeletal muscle and heart cells (35,36), it has been hypothesized that MBNL1 depletion occurring as a consequence of aberrant sequestration, is a key mechanism that underlies the functional inactivation of MBNL1 in DM1.
Gene_expression (depletion) of MBNL1 in heart
19) Confidence 0.63 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.22 Pain Relevance 0
To estimate the amount of MBNL1 present in the nucleus, the cytoplasm and the foci, the fluorescence signals (areaƗintensity) were measured using IP Lab software (Scanalytics Inc., USA).
Gene_expression (present) of MBNL1 in nucleus
20) Confidence 0.63 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.06 Pain Relevance 0

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