INT211027

Context Info Confidence 0.78 First Reported 2007 Last Reported 2007 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 10 Disease Relevance 4.72 Pain Relevance 0.82

mRNA binding (Celf4) mRNA processing (Celf4) RNA binding (Celf4) nucleus (Celf4) cytoplasm (Celf4)

Anatomy Link Frequency hippocampus 3 brain 2 Celf4 (Mus musculus)

Pain Link Frequency Relevance Heat Hippocampus 100 99.86 Pyramidal cell 30 99.48 Neurotransmitter 10 97.04 cerebral cortex 20 88.32 Serotonin 30 74.96 Neuronal excitability 10 44.72 fluoxetine 20 5.00 Analgesic 10 5.00

Disease Link Frequency Relevance Heat Absence Epilepsy 50 99.92 Convulsion 530 99.42 Epilepsy 210 96.32 Targeted Disruption 70 90.56 Disease 50 88.84 Attention Deficit Hyperactivity Disorder 20 87.52 Obesity 10 85.20 Weight Gain 20 77.68 Inborn Genetic Diseases 10 72.76 Sprains And Strains 90 72.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

We then evaluated the impact of transgene insertion on Brunol4 expression.

Gene_expression (expression) of Brunol4

1) Confidence 0.78 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1934399 Disease Relevance 0.26 Pain Relevance 0

The down-regulation of each was confirmed in adults, and was greatest in the hippocampus, where Brunol4 expression is high.

Gene_expression (expression) of Brunol4 in hippocampus associated with hippocampus

2) Confidence 0.78 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1934399 Disease Relevance 0.81 Pain Relevance 0.05

These region-specific decreases before the onset of seizures were consistent with the limbic-seizure phenotype and the overlapping hippocampal expression of the four genes with that of Brunol4.

Gene_expression (expression) of Brunol4 associated with convulsion

3) Confidence 0.78 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1934399 Disease Relevance 0.72 Pain Relevance 0.15

All four molecules have been found in the pyramidal neurons in the hippocampus where Brunol4 is highly expressed [25–28].

Gene_expression (expressed) of Brunol4 in hippocampus associated with pyramidal cell and hippocampus

4) Confidence 0.78 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1934399 Disease Relevance 0.33 Pain Relevance 0.20

Only brain samples showed robust signal, despite prolonged exposure time, suggesting that BRUNOL4 is brain specific in adults (Figure 3C), consistent with a recent survey of organ protein expression in mice that detected BRUNOL4 only in the brain [19].

Gene_expression (detected) of BRUNOL4 in brain

5) Confidence 0.68 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1934399 Disease Relevance 0.13 Pain Relevance 0.19

Brunol4 is widely expressed in the brain with enrichment in the hippocampus.

Gene_expression (expressed) of Brunol4 in hippocampus associated with hippocampus

6) Confidence 0.68 Published 2007 Journal PLoS Genetics Section Abstract Doc Link PMC1934399 Disease Relevance 0.72 Pain Relevance 0.09

Expression analysis of the neighboring genes with potential brain function did not reveal difference between Ff/Ff homozygous mutants and normal controls (unpublished data), suggesting that Brunol4 is the only brain-expressed gene affected by the transgene insertion.

Gene_expression (expressed) of Brunol4 in brain

7) Confidence 0.60 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1934399 Disease Relevance 0.08 Pain Relevance 0

In this study we describe the seizure phenotypes of mice carrying Brunol4 disruption, and begin to explore the molecular consequences using gene expression profiling and genetic interaction tests.

Gene_expression (disruption) of Brunol4 associated with convulsion

8) Confidence 0.59 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1934399 Disease Relevance 0.53 Pain Relevance 0

Here we describe the disruption of the expression of an RNA-binding protein, BRUNOL4 (Bruno-like 4) leading to partial limbic and tonic–clonic seizures in a new mouse model of epilepsy called “frequent-flyer” (abbreviated Ff; gene symbol: Brunol4Ff).

Gene_expression (expression) of BRUNOL4 associated with epilepsy and convulsion

9) Confidence 0.52 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1934399 Disease Relevance 1.03 Pain Relevance 0.05

In order to evaluate the expression pattern of Brunol4 in adults, we examined RNA from a variety of tissues.

Gene_expression (expression) of Brunol4

10) Confidence 0.52 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1934399 Disease Relevance 0.09 Pain Relevance 0.09

General Comments

This test has worked.