INT55709

Context Info Confidence 0.51 First Reported 1994 Last Reported 2010 Negated 0 Speculated 2 Reported most in Body Documents 7 Total Number 9 Disease Relevance 1.28 Pain Relevance 1.60

transport (Gria4) plasma membrane (Gria4)

Anatomy Link Frequency dendrites 1 spinal 1 cerebellum 1 Gria4 (Mus musculus)

Pain Link Frequency Relevance Heat Analgesic 8 99.80 Enkephalin 3 99.80 nociceptor 1 99.80 antinociception 2 99.52 Opioid 1 95.28 Action potential 33 94.92 Nav1.6 11 93.12 Nav1.2 11 92.08 sodium channel 17 91.80 opioid receptor 8 91.56

Disease Link Frequency Relevance Heat Epilepsy 14 96.28 Absence Epilepsy 105 95.92 Sprains And Strains 140 95.44 Targeted Disruption 63 95.44 Convulsion 35 79.32 Ataxia 35 15.04 Congenital Anomalies 14 5.00 Generalized Epilepsy 14 5.00 Death 7 5.00 Dislocations 7 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In addition, loss of Gria4 during development may have led to compensatory mechanisms.

Negative_regulation (loss) of Gria4

1) Confidence 0.51 Published 2008 Journal Human Molecular Genetics Section Body Doc Link PMC2405903 Disease Relevance 0.24 Pain Relevance 0

Together these data show that a genetic deficiency in Gria4, whether reduction (Gria4spkw1 allele) or complete lack (Gria4tm1Dgen allele), is associated with a high frequency of SWD, modeling absence epilepsy.

Spec (whether) Negative_regulation (deficiency) of Gria4 associated with absence epilepsy

2) Confidence 0.51 Published 2008 Journal Human Molecular Genetics Section Body Doc Link PMC2405903 Disease Relevance 0.09 Pain Relevance 0

The association of Gria4 deficiency with a high rate of SWD is also interesting in view of stargazer mice, which have a similar epileptic phenotype along with other neurological impairments (43,44).

Negative_regulation (deficiency) of Gria4 associated with epilepsy

3) Confidence 0.43 Published 2008 Journal Human Molecular Genetics Section Body Doc Link PMC2405903 Disease Relevance 0.24 Pain Relevance 0

Furthermore, decrease in transcript levels was accompanied by a significant reduction in the amount of GluR4 protein in HeJ cerebellum compared with control (Fig. 3C)—suggesting that HeJ carries a severely hypomorphic allele of Gria4.

Negative_regulation (reduction) of GluR4 in cerebellum

4) Confidence 0.43 Published 2008 Journal Human Molecular Genetics Section Body Doc Link PMC2405903 Disease Relevance 0.22 Pain Relevance 0

To confirm the causal relationship between Gria4 deficiency and SWD, we assessed the electroencephalographic phenotype of an independent mutation of Gria4: the Gria4tm1Dgen knockout allele (expression defect data are shown in Figure 3B and C; see Materials and Methods for more details on the origin and nature of Gria4tm1Dgen).

Negative_regulation (deficiency) of Gria4 associated with targeted disruption

5) Confidence 0.43 Published 2008 Journal Human Molecular Genetics Section Body Doc Link PMC2405903 Disease Relevance 0.23 Pain Relevance 0

Together these data show that a genetic deficiency in Gria4, whether reduction (Gria4spkw1 allele) or complete lack (Gria4tm1Dgen allele), is associated with a high frequency of SWD, modeling absence epilepsy.

Spec (whether) Negative_regulation (reduction) of Gria4spkw1 associated with absence epilepsy

6) Confidence 0.38 Published 2008 Journal Human Molecular Genetics Section Body Doc Link PMC2405903 Disease Relevance 0.10 Pain Relevance 0

The striking increase of SWD in Gria4spkw1 homozygous backcross mice compared with Gria4spkw1 homozygous HeJ parents (?

Negative_regulation (backcross) of Gria4spkw1

7) Confidence 0.37 Published 2008 Journal Human Molecular Genetics Section Body Doc Link PMC2405903 Disease Relevance 0.16 Pain Relevance 0

Selective inhibition of [D-Ala2, Glu4]deltorphin antinociception by supraspinal, but not spinal, administration of an antisense oligodeoxynucleotide to an opioid delta receptor.

Negative_regulation (inhibition) of Glu4 in spinal associated with antinociception, analgesic and opioid

8) Confidence 0.02 Published 1994 Journal Life Sci. Section Title Doc Link 8015351 Disease Relevance 0 Pain Relevance 1.15

Observed backpropagation characteristics such as reduction in spike amplitude and failure of antidromic transmission of APs into dendrites as well as findings on spike initiation sites can be explained by the distribution of low-threshold Nav1.6 and high-threshold Nav1.2 sodium channels in pyramidal cells (Stuart et al., 1997; Yu et al., 2008; Hu et al., 2009).

Negative_regulation (reduction) of spike in dendrites associated with pyramidal cell, sodium channel, nav1.2 and nav1.6

9) Confidence 0.01 Published 2010 Journal Neuroscience Section Body Doc Link PMC2954315 Disease Relevance 0 Pain Relevance 0.44

General Comments

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