INT277526

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Context Info
Confidence 0.78
First Reported 2009
Last Reported 2009
Negated 5
Speculated 1
Reported most in Body
Documents 1
Total Number 72
Disease Relevance 29.02
Pain Relevance 0.17

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Anatomy Link Frequency
retina 19
photoreceptors 12
glial cell 3
cochlear 2
adult mouse 2
Clrn1 (Mus musculus)
Pain Link Frequency Relevance Heat
Glutamate 72 80.32 Quite High
imagery 72 77.68 Quite High
ketamine 144 48.40 Quite Low
anesthesia 72 47.80 Quite Low
medulla 216 43.60 Quite Low
Disease Link Frequency Relevance Heat
Retina Disease 2592 100.00 Very High Very High Very High
Usher Syndrome 2592 100.00 Very High Very High Very High
Deafness 1008 100.00 Very High Very High Very High
Blindness 576 100.00 Very High Very High Very High
Targeted Disruption 4896 99.96 Very High Very High Very High
Disease 648 99.16 Very High Very High Very High
Disease Progression 72 98.48 Very High Very High Very High
Ganglion Cysts 288 98.24 Very High Very High Very High
Sprains And Strains 72 97.68 Very High Very High Very High
Hearing Impairment 144 96.08 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Similar to findings in the inner ear [12], Clrn1 expression is noted at all developmental ages tested, with slightly higher expression levels observed in the E15 animal (both embryo and whole head samples; Figure 1E).
Gene_expression (expression) of Clrn1 in head
1) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0 Pain Relevance 0
Clrn1 is clearly expressed in the eyes (and retinas) of animals before birth.
Gene_expression (expressed) of Clrn1 in retinas
2) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0 Pain Relevance 0
If CLRN1 expression in humans is comparable to the expression pattern observed in mice, this is the first report of an inner retinal protein that, when mutated, causes retinal degeneration.


Gene_expression (expression) of CLRN1 associated with retina disease
3) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Abstract Doc Link PMC2719914 Disease Relevance 1.02 Pain Relevance 0
Clrn1 ISH was clearly detectable at P7 in the INL (Figure 2G).
Gene_expression (detectable) of Clrn1
4) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.53 Pain Relevance 0
4-fold apparent increase in Clrn1 expression when photoreceptors are absent from the mutant retinal samples.
Gene_expression (expression) of Clrn1 in photoreceptors
5) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.07 Pain Relevance 0
The discovery that Clrn1 is expressed in a developmentally regulated manner in Müller cells, and that Clrn1 is not expressed in photoreceptors, was unexpected.
Neg (not) Gene_expression (expressed) of Clrn1 in photoreceptors
6) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.60 Pain Relevance 0
Transfection with the EGFP-CLRN1 construct was performed essentially as described previously [72].
Gene_expression (Transfection) of EGFP-CLRN1
7) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.05 Pain Relevance 0
If these data hold true in humans, they imply that CLRN1 is expressed in the INL and that proteins expressed in the inner retina, and specifically in Müller cells, can cause RP.
Gene_expression (expressed) of CLRN1 in retina associated with retina disease
8) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.66 Pain Relevance 0
Our original hypothesis stated that Clrn1 would be expressed in photoreceptors, and that the protein, CLRN1, would be targeted to rod photoreceptor synapses and contribute to synaptic adhesion and/or structure.
Gene_expression (expressed) of Clrn1 in photoreceptors associated with adhesions
9) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.74 Pain Relevance 0
To follow up on inner retinal localization of Clrn1 by ISH in WT retinal tissue (Figure 3), we performed immunohistochemistry to clarify which retinal cell type(s) express Clrn1.
Gene_expression (express) of Clrn1
10) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.17 Pain Relevance 0
Indeed, recent immunohistochemical evidence purports CLRN1 to be localized to photoreceptors [24], and it remains unclear how to harmonize these data with our findings presented here, where we show that Clrn1 is not expressed in photoreceptors.
Neg (not) Gene_expression (expressed) of Clrn1 in photoreceptors
11) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.73 Pain Relevance 0
However, Clrn1 expression is subsequently down-regulated (Figure 2I) and not detectable by 4 weeks of age in WT mouse retina (Figure 2K), although all ages show expression by end-point PCR (Figure 1).
Gene_expression (expression) of Clrn1 in retina
12) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.46 Pain Relevance 0
Two antibodies (one developed in rabbit, one in chicken) accurately detected an EGFP-CLRN1 fusion protein transiently expressed by HEK293 cells (Figure S4).
Gene_expression (expressed) of EGFP-CLRN1
13) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.31 Pain Relevance 0
Further supporting this unusual finding is the fact that aged animals (C3H mice, RCS rats, and P23H-3 rats) that have completely lost their photoreceptors continue to express Clrn1 at WT levels.
Gene_expression (express) of Clrn1 in photoreceptors
14) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.58 Pain Relevance 0
LCM localized Clrn1 transcripts to the retinas inner nuclear layer, and WT levels of retinal Clrn1 expression were observed in photoreceptor-less retinas.
Gene_expression (expression) of Clrn1 in retinas
15) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Abstract Doc Link PMC2719914 Disease Relevance 0.88 Pain Relevance 0
Immunocytochemical detection of CLRN1 protein in retinal tissues has not been successful.
Gene_expression (detection) of CLRN1 protein
16) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.27 Pain Relevance 0
The apparent increase in Clrn1 expression is due to the loss of the photoreceptor RNA contribution to the total RNA samples from mutant animals when equal amounts (from WT and mutant retinas) were included in the amplification reactions.
Gene_expression (expression) of Clrn1 in retinas
17) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.09 Pain Relevance 0
In this case, the mouse cochlea would remain sensitive to either the absence (KO) or mutation (point mutation or truncation) of CLRN1, whereas the retina would be insensitive in the KO condition, but would degenerate when mutant CLRN1 proteins are expressed.
Gene_expression (expressed) of CLRN1 in retina associated with targeted disruption
18) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.29 Pain Relevance 0
When equivalent total amounts of whole retinal cDNA were PCR amplified (without normalization), P23H-3 and RCS retinal samples show a relative increase in Clrn1 expression compared to control retinas.
Gene_expression (expression) of Clrn1 in retinas
19) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.09 Pain Relevance 0
The discovery that Clrn1 is expressed in a developmentally regulated manner in Müller cells, and that Clrn1 is not expressed in photoreceptors, was unexpected.
Gene_expression (expressed) of Clrn1 in photoreceptors
20) Confidence 0.78 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2719914 Disease Relevance 0.63 Pain Relevance 0

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