INT277283

Context Info Confidence 0.49 First Reported 2009 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 6 Disease Relevance 0.68 Pain Relevance 0.62

transport (Slc6a11) cytoplasm (Slc6a11)

Anatomy Link Frequency synapse 4 Slc6a11 (Mus musculus)

Pain Link Frequency Relevance Heat GABAergic 60 98.16 gABA 54 97.82 imagery 60 76.48 interneuron 6 5.00 anesthesia 6 5.00 medulla 6 5.00

Disease Link Frequency Relevance Heat Targeted Disruption 120 82.00 Urological Neuroanatomy 6 81.88 Frailty 126 80.72 Sprains And Strains 12 55.68 Spinocerebellar Ataxia Type 2 30 50.00 Neuroblastoma 6 43.44 Peripheral Arterial Disease 24 23.28 Disease 66 5.00 Neurodegenerative Disease 12 5.00 Huntington's Chorea 12 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

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 GABT4 associated with gabaergic

1) Confidence 0.49 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.08 Pain Relevance 0.05

Since Gabt4 was identified as a putative target of CUGBP1 by CLIP analysis and because increased Gabt4 expression could explain the increased cortical loss of GABAergic inhibition previously reported in our mice by reducing GABA at the synapse, we hypothesized that SCA8 CUGexp RNA dysregulates Cugbp1 and Mbnl1 pathways resulting in an increase in Gabt4 expression.

Positive_regulation (increased) of Gene_expression (expression) of Gabt4 in synapse associated with gaba and gabaergic

2) Confidence 0.49 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.06 Pain Relevance 0.26

Because exon 7 of Gabt4 was identified as a potential Cugbp1 binding site, we investigated if increases in GABT4 expression could be related to misregulation of exon 7 alternative splicing.

Positive_regulation (increases) of Gene_expression (expression) of GABT4

3) Confidence 0.49 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.13 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.

Positive_regulation (trigger) of Gene_expression (expression) of GABT4 associated with gabaergic

4) Confidence 0.49 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.08 Pain Relevance 0.05

Since Gabt4 was identified as a putative target of CUGBP1 by CLIP analysis and because increased Gabt4 expression could explain the increased cortical loss of GABAergic inhibition previously reported in our mice by reducing GABA at the synapse, we hypothesized that SCA8 CUGexp RNA dysregulates Cugbp1 and Mbnl1 pathways resulting in an increase in Gabt4 expression.

Positive_regulation (increase) of Gene_expression (expression) of Gabt4 in synapse associated with gaba and gabaergic

5) Confidence 0.49 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.25 Pain Relevance 0.24

Similar to humans, Gabt4 is also up-regulated in the SCA8 BAC-Exp and Mbnl1?

Positive_regulation (up) of Gene_expression (is) of Gabt4

6) Confidence 0.49 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719092 Disease Relevance 0.08 Pain Relevance 0

General Comments

This test has worked.