INT151539

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Context Info
Confidence 0.59
First Reported 2007
Last Reported 2009
Negated 0
Speculated 0
Reported most in Body
Documents 9
Total Number 22
Disease Relevance 11.85
Pain Relevance 0.87

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

transport (Fmr1) RNA binding (Fmr1) nucleus (Fmr1)
cytoplasm (Fmr1)
Anatomy Link Frequency
brain 2
neuronal 1
Mouse 1
neurons 1
Fmr1 (Mus musculus)
Fmr1 - I304N (6)
Pain Link Frequency Relevance Heat
Glutamate receptor 54 98.48 Very High Very High Very High
addiction 3 88.00 High High
Lasting pain 3 86.80 High High
Anterior cingulate cortex 15 63.60 Quite High
Hippocampus 33 23.36 Low Low
cerebral cortex 5 22.84 Low Low
agonist 113 5.00 Very Low Very Low Very Low
alcohol 14 5.00 Very Low Very Low Very Low
antagonist 14 5.00 Very Low Very Low Very Low
depression 14 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Intellectual Impairment 159 100.00 Very High Very High Very High
Disease 126 99.76 Very High Very High Very High
Syndrome 183 99.66 Very High Very High Very High
Autism 86 99.40 Very High Very High Very High
Aging 15 99.28 Very High Very High Very High
Targeted Disruption 331 99.16 Very High Very High Very High
Congenital Anomalies 47 98.46 Very High Very High Very High
Developmental Disabilities 5 97.76 Very High Very High Very High
Fragile X Syndrome 294 97.12 Very High Very High Very High
Convulsion 61 96.52 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In summary, our behavioral assays of Fmr1I304N mice indicate that they show abnormalities in the same tests, in the same direction, and to similar levels in all assays previously performed in our laboratory (Table 1), strongly supporting the conclusion that the I304N mutation is sufficient to phenocopy loss of the Fmr1 gene.
Negative_regulation (loss) of Fmr1 associated with congenital anomalies
1) Confidence 0.59 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.46 Pain Relevance 0.05
This finding suggests that loss of FMRP activity, including but not necessarily limited to KH2 RNA binding, may play a critical role in leading to the synaptic defects evident in the mouse, and, presumably, in human patients.
Negative_regulation (loss) of FMRP
2) Confidence 0.59 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0
I304N FMRP is defective in polyribosome association and RNA binding
Negative_regulation (defective) of I304N FMRP (I304N)
3) Confidence 0.59 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0
Interestingly, the decrease in I304N FMRP levels is much more pronounced in mice at P14, relative to older mice (Figure 4A and 4B).
Negative_regulation (decrease) of I304N FMRP (I304N)
4) Confidence 0.59 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.11 Pain Relevance 0
To assess whether the loss of I304N-FMRP from larger complexes might result from a loss of protein-RNA interaction, we treated brain cytoplasmic extracts with excess RNase prior to Superose 6 gel filtration.
Negative_regulation (loss) of I304N-FMRP (I304N) in brain
5) Confidence 0.59 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0
The fragile X syndrome is caused by the lack of fragile X mental retardation protein (FMRP) attributable to silencing of the FMR1 gene.
Negative_regulation (lack) of FMRP associated with intellectual impairment and syndrome
6) Confidence 0.56 Published 2008 Journal J. Neurosci. Section Abstract Doc Link 18434517 Disease Relevance 0.51 Pain Relevance 0.27
The post-transcriptional reduction in steady state levels of I304N-FMRP compared with mRNA levels has also been observed in two lines of I304N-FMRP BAC transgenic mice (data not shown), and in I307N-dfmr1 flies, which have the analogous mutation to I304N-FMRP in mammals [77].
Negative_regulation (reduction) of I304N-FMRP (I304N) associated with targeted disruption
7) Confidence 0.51 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.29 Pain Relevance 0
These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder.


Negative_regulation (loss) of FMRP associated with fragile x syndrome
8) Confidence 0.43 Published 2009 Journal PLoS Genetics Section Abstract Doc Link PMC2779495 Disease Relevance 0.77 Pain Relevance 0
Nonetheless, based on our finding of decreased I304N FMRP in the mouse model and similar results from the I307N mutation in dfmr1 [77], we infer that it is most likely that the I304N patient has lower steady state levels of neuronal I304N-FMRP.


Negative_regulation (decreased) of I304N FMRP (I304N) in neuronal
9) Confidence 0.43 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.77 Pain Relevance 0
The I304N mutation causes defective KH2-mediated RNA binding in neurons, and decreased FMRP levels, particularly in younger animals.
Negative_regulation (decreased) of FMRP in neurons
10) Confidence 0.43 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.46 Pain Relevance 0
Such mutations have not generally been of help in understanding the devastating effects of the loss of function of the Fragile X mental retardation protein (FMRP), which include complex behavioral deficits including mental retardation, autism, and seizures [6].
Negative_regulation (loss) of FMRP associated with convulsion, autism and intellectual impairment
11) Confidence 0.43 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.88 Pain Relevance 0
Steady-state levels of endogenous I304N-FMRP were found to be decreased relative to WT FMRP.
Negative_regulation (decreased) of WT FMRP
12) Confidence 0.43 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.23 Pain Relevance 0
Therefore a major biochemical defect in the Fmr1I304N mouse is the loss of KH2-dependent RNA binding.
Negative_regulation (defect) of Fmr1I304N
13) Confidence 0.43 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.14 Pain Relevance 0
Evaluation at earlier times revealed that the APP mRNA–FMRP complex was lost within 5 min of DHPG treatment (unpublished data).
Negative_regulation (lost) of FMRP
14) Confidence 0.42 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1808499 Disease Relevance 0.20 Pain Relevance 0
The molecular basis for defective pruning in fmr-1 KO mice is unknown, but likely reflects the loss of FMRP-regulated translation of synaptic mRNA.
Negative_regulation (loss) of FMRP associated with targeted disruption
15) Confidence 0.42 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1808499 Disease Relevance 0.75 Pain Relevance 0
In addition, FMRP mRNA and protein expression are downregulated as a function of aging in the mouse brain [56], suggesting that repressed transcripts, such as APP, would be upregulated with aging, a well-known phenomenon in animals and humans.
Negative_regulation (downregulated) of FMRP mRNA in brain associated with aging
16) Confidence 0.42 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1808499 Disease Relevance 1.97 Pain Relevance 0
The fragile X syndrome is caused by the lack of fragile X mental retardation protein (FMRP) attributable to silencing of the FMR1 gene.
Negative_regulation (silencing) of FMR1 gene associated with intellectual impairment and syndrome
17) Confidence 0.41 Published 2008 Journal J. Neurosci. Section Abstract Doc Link 18434517 Disease Relevance 0.52 Pain Relevance 0.28
A Mouse Model of the Human Fragile X Syndrome I304N Mutation

The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA–binding protein FMRP.

Negative_regulation (loss) of FMRP in Mouse associated with autism, intellectual impairment, syndrome, congenital anomalies and fragile x syndrome
18) Confidence 0.38 Published 2009 Journal PLoS Genetics Section Title Doc Link PMC2779495 Disease Relevance 0.97 Pain Relevance 0
Steady-state levels of endogenous I304N-FMRP were found to be decreased relative to WT FMRP.
Negative_regulation (decreased) of I304N-FMRP (I304N)
19) Confidence 0.38 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.23 Pain Relevance 0
The CGG expansion is associated with hypermethylation of the surrounding DNA, chromatin condensation, and subsequent transcriptional silencing of the fmr-1 gene, resulting in the loss of expression of fragile X mental retardation protein (FMRP) [7].
Negative_regulation (loss) of retardation protein associated with intellectual impairment
20) Confidence 0.36 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1808499 Disease Relevance 1.05 Pain Relevance 0

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