INT255113

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Context Info
Confidence 0.69
First Reported 2008
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 15
Total Number 15
Disease Relevance 3.28
Pain Relevance 0.47

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 5
heart 3
eye 2
myoblasts 2
muscle 2
Mbnl1 (Mus musculus)
Pain Link Frequency Relevance Heat
gABA 63 99.08 Very High Very High Very High
GABAergic 70 94.68 High High
imagery 74 94.08 High High
anticonvulsant 1 43.76 Quite Low
Pain 1 42.16 Quite Low
Kinase C 5 26.08 Quite Low
anesthesia 15 5.00 Very Low Very Low Very Low
tolerance 14 5.00 Very Low Very Low Very Low
interneuron 7 5.00 Very Low Very Low Very Low
medulla 7 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Frailty 182 98.88 Very High Very High Very High
Disease 133 97.32 Very High Very High Very High
Hypopituitarism 50 96.28 Very High Very High Very High
Congenital Anomalies 48 94.28 High High
Targeted Disruption 253 93.96 High High
Arrhythmia Under Development 13 84.60 Quite High
Spinocerebellar Ataxia Type 2 35 78.08 Quite High
Cataract 21 76.48 Quite High
Arrhythmias 2 Under Development 36 69.24 Quite High
Neurological Disease 7 68.68 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
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.
Positive_regulation (overexpression) of Gene_expression (overexpression) of MBNL1 in skeletal muscle
1) Confidence 0.69 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.25 Pain Relevance 0.07
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].
Positive_regulation (overexpression) of Gene_expression (overexpression) of Mbnl1 in skeletal muscle
2) Confidence 0.60 Published 2010 Journal Current Chemical Genomics Section Body Doc Link PMC2874217 Disease Relevance 0.36 Pain Relevance 0
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).
Positive_regulation (increased) of Gene_expression (expression) of CUGBP1-MBNL1 in brain associated with gaba
3) Confidence 0.50 Published 2009 Journal PLoS Genetics Section Abstract Doc Link PMC2719092 Disease Relevance 0.22 Pain Relevance 0.14
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.
Positive_regulation (overexpression) of Gene_expression (overexpression) of MBNL1 in SK-N-SH
4) Confidence 0.50 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.08 Pain Relevance 0.08
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.
Positive_regulation (trigger) of Gene_expression (expression) of CUGBP1-MBNL1 associated with gabaergic
5) Confidence 0.50 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.08 Pain Relevance 0.05
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.
Positive_regulation (increased) of Gene_expression (expression) of CUGBP1-MBNL1 associated with gabaergic
6) Confidence 0.50 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.08 Pain Relevance 0.05
Similar to humans, Gabt4 is also up-regulated in the SCA8 BAC-Exp and Mbnl1?
Positive_regulation (up) of Gene_expression (is) of Mbnl1
7) Confidence 0.50 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.08 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.
Positive_regulation (occurring) of Gene_expression (depletion) of MBNL1 in heart
8) Confidence 0.47 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.22 Pain Relevance 0
Thus these results demonstrate that cytoplasmic CUG foci, although more diffuse in appearance, can effectively sequester Mbnl1 in vivo.


Positive_regulation (sequester) of Gene_expression (sequester) of Mbnl1
9) Confidence 0.47 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0 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].
Positive_regulation (sufficient) of Gene_expression (expression) of MBNL1 in myoblasts
10) Confidence 0.47 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0 Pain Relevance 0
From a therapeutic viewpoint, it is promising that this change is reversed in cells overexpressing MBNL1.



Positive_regulation (overexpressing) of Gene_expression (overexpressing) of MBNL1
11) Confidence 0.46 Published 2009 Journal PLoS Genetics Section Abstract Doc Link PMC2719092 Disease Relevance 0.24 Pain Relevance 0.09
Botas’ lab), interrupted CUG repeats (CUG20CUCGA24) cause muscle wasting and eye degeneration; and this phenotype is rescued by overexpression of MBNL1 [57].
Positive_regulation (overexpression) of Gene_expression (overexpression) of MBNL1 in eye associated with frailty
12) Confidence 0.41 Published 2010 Journal Current Genomics Section Body Doc Link PMC2874224 Disease Relevance 0.44 Pain Relevance 0
Although surprising, the authors explained the DM1 phenotype by the unbalance between CUG-BP1 (upregulated) and Mbnl1 (unchanged) antagonistic activities as alternative splicing regulators resulting in missplicing of characteristic transcripts such as ClC-1 and cTNT [72].
Positive_regulation (upregulated) of Gene_expression (phenotype) of Mbnl1
13) Confidence 0.39 Published 2008 Journal Current Genomics Section Body Doc Link PMC2694559 Disease Relevance 0.41 Pain Relevance 0
Conversely, overexpression of MBNL1 in vivo using a recombinant adeno-associated viral vector rescued disease-associated muscle myotonia and adult-splicing patterns of muscle pre-mRNAs characteristically misspliced in transgenic mice expressing 250 CTG repeats in the 3´UTR of a human skeletal alpha-actin transcript.
Positive_regulation (overexpression) of Gene_expression (overexpression) of MBNL1 in muscle associated with targeted disruption, hypopituitarism and disease
14) Confidence 0.39 Published 2008 Journal Current Genomics Section Body Doc Link PMC2694559 Disease Relevance 0.60 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.
Positive_regulation (occurring) of in skeletal muscle Gene_expression (depletion) of MBNL1 in heart
15) Confidence 0.16 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597774 Disease Relevance 0.22 Pain Relevance 0

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