| Title |
Gain-of-function mutation in Gnao1: A murine model of epileptiform encephalopathy (EIEE17)?
|
|---|---|
| Published in |
Mammalian Genome, April 2014
|
| DOI | 10.1007/s00335-014-9509-z |
| Pubmed ID | |
| Authors |
Jason M. Kehrl, Kinshuk Sahaya, Hans M. Dalton, Raelene A. Charbeneau, Kevin T. Kohut, Kristen Gilbert, Madeline C. Pelz, Jack Parent, Richard R. Neubig |
| Abstract |
G protein-coupled receptors strongly modulate neuronal excitability but there has been little evidence for G protein mechanisms in genetic epilepsies. Recently, four patients with epileptic encephalopathy (EIEE17) were found to have mutations in GNAO1, the most abundant G protein in brain, but the mechanism of this effect is not known. The GNAO1 gene product, Gαo, negatively regulates neurotransmitter release. Here, we report a dominant murine model of Gnao1-related seizures and sudden death. We introduced a genomic gain-of-function knock-in mutation (Gnao1 (+/G184S)) that prevents Go turnoff by Regulators of G protein signaling proteins. This results in rare seizures, strain-dependent death between 15 and 40 weeks of age, and a markedly increased frequency of interictal epileptiform discharges. Mutants on a C57BL/6J background also have faster sensitization to pentylenetetrazol (PTZ) kindling. Both premature lethality and PTZ kindling effects are suppressed in the 129SvJ mouse strain. We have mapped a 129S-derived modifier locus on Chromosome 17 (within the region 41-70 MB) as a Modifer of G protein Seizures (Mogs1). Our mouse model suggests a novel gain-of-function mechanism for the newly defined subset of epileptic encephalopathy (EIEE17). Furthermore, it reveals a new epilepsy susceptibility modifier Mogs1 with implications for the complex genetics of human epilepsy as well as sudden death in epilepsy. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Scientists | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 36 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 28% |
| Researcher | 7 | 19% |
| Student > Doctoral Student | 2 | 6% |
| Student > Bachelor | 2 | 6% |
| Student > Master | 2 | 6% |
| Other | 4 | 11% |
| Unknown | 9 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 28% |
| Agricultural and Biological Sciences | 5 | 14% |
| Biochemistry, Genetics and Molecular Biology | 4 | 11% |
| Neuroscience | 3 | 8% |
| Unspecified | 1 | 3% |
| Other | 3 | 8% |
| Unknown | 10 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 April 2014.
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#17,719,424
of 22,753,345 outputs
Outputs from Mammalian Genome
#979
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Outputs of similar age
#156,111
of 226,065 outputs
Outputs of similar age from Mammalian Genome
#63
of 68 outputs
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