Mutation analysis of the inwardly rectifying K+ channels KCNJ6 (GIRK2) and KCNJ3 (GIRK1) in juvenile myoclonic epilepsy

Hallmann, Kerstin; Durner, Martina; Sander, Thomas; Steinlein, Ortrud K.

doi:10.1002/(sici)1096-8628(20000207)96:1<8::aid-ajmg3>3.0.co;2-s

Cited by 14 publications

(5 citation statements)

References 39 publications

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“…Among those genes, Kcnj6 ( Girk2 ) codes for a ion channel subunit, ion channels representing 66% of the currently known Mendelian human epilepsy gene, and a point mutation in this gene causes ataxia, tremor and tonico-clonic seizures in the weaver mouse [81]. However, studies in human have so far failed to demonstrate an association between KCNJ6 and epilepsy [82], [83]. Dscam , a member of the immunoglobulin (Ig) superfamily, has been implicated in cell migration and sorting, axon guidance, formation of neural connections and synaptic plasticity [84], [85].…”

Section: Discussionmentioning

confidence: 99%

Characterization of PTZ-Induced Seizure Susceptibility in a Down Syndrome Mouse Model That Overexpresses CSTB

et al. 2011

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Down syndrome (DS) is a complex genetic syndrome characterized by intellectual disability, dysmorphism and variable additional physiological traits. Current research progress has begun to decipher the neural mechanisms underlying cognitive impairment, leading to new therapeutic perspectives. Pentylenetetrazol (PTZ) has recently been found to have positive effects on learning and memory capacities of a DS mouse model and is foreseen to treat DS patients. But PTZ is also known to be a convulsant drug at higher dose and DS persons are more prone to epileptic seizures than the general population. This raises concerns over what long-term effects of treatment might be in the DS population. The cause of increased propensity for epilepsy in the DS population and which Hsa21 gene(s) are implicated remain unknown. Among Hsa21 candidate genes in epilepsy, CSTB, coding for the cystein protease inhibitor cystatin B, is involved in progressive myoclonus epilepsy and ataxia in both mice and human. Thus we aim to evaluate the effect of an increase in Cstb gene dosage on spontaneous epileptic activity and susceptibility to PTZ-induced seizure. To this end we generated a new mouse model trisomic for Cstb by homologous recombination. We verified that increasing copy number of Cstb from Trisomy (Ts) to Tetrasomy (Tt) was driving overexpression of the gene in the brain, we checked transgenic animals for presence of locomotor activity and electroencephalogram (EEG) abnormalities characteristic of myoclonic epilepsy and we tested if those animals were prone to PTZ-induced seizure. Overall, the results of the analysis shows that an increase in Cstb does not induce any spontaneous epileptic activity and neither increase or decrease the propensity of Ts and Tt mice to myoclonic seizures suggesting that Ctsb dosage should not interfere with PTZ-treatment.

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Section: Discussionmentioning

confidence: 99%

Characterization of PTZ-Induced Seizure Susceptibility in a Down Syndrome Mouse Model That Overexpresses CSTB

et al. 2011

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“…A knockout mouse model found that animals deprived of functional KCNJ6 protein were susceptible to spontaneous and provoked seizures (cf. Hallmann et al, 2000). A recent study with a mouse model of seizure activity reported that GIRK2 channel ( KCNJ6 ) may play a major role in the genesis of childhood epilepsy (infantile spasms) as measured by the changes in EEG activity and behavior (Blichowski et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

A KCNJ6 gene polymorphism modulates theta oscillations during reward processing

Kamarajan

Pandey

Chorlian

et al. 2017

International Journal of Psychophysiology

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Event related oscillations (EROs) are heritable measures of neurocognitive function that have served as useful phenotype in genetic research. A recent family genome-wide association study (GWAS) by the Collaborative Study on the Genetics of Alcoholism (COGA) found that theta EROs during visual target detection were associated at genome-wide levels with several single nucleotide polymorphisms (SNPs), including a synonymous SNP, rs702859, in the KCNJ6 gene that encodes GIRK2, a G-protein inward rectifying potassium channel that regulates excitability of neuronal networks. The present study examined the effect of the KCNJ6 SNP (rs702859), previously associated with theta ERO to targets in a visual oddball task, on theta EROs during reward processing in a monetary gambling task. The participants were 1,601 adolescent and young adult offspring within the age-range of 17–25 years (800 males and 801 females) from high-dense alcoholism families as well as control families of the COGA prospective study. Theta ERO power (3.5–7.5 Hz, 200–500 ms post-stimulus) was compared across genotype groups. ERO theta power at central and parietal regions increased as a function of the minor allele (A) dose in the genotype (AA > AG > GG) in both loss and gain conditions. These findings indicate that variations in the KCNJ6 SNP influence magnitude of theta oscillations at posterior loci during the evaluation of loss and gain, reflecting a genetic influence on neuronal circuits involved in reward-processing. Increased theta power as a function of minor allele dose suggests more efficient cognitive processing in those carrying the minor allele of the KCNJ6 SNPs. Future studies are needed to determine the implications of these genetic effects on posterior theta EROs as possible “protective” factors, or as indices of delays in brain maturation (i.e., lack of frontalization).

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“…Mutation analysis of genes encoding Kir3.1 and Kir3.2 channels was performed in 38 patients with juvenile myoclonic epilepsy (JME). However, novel identified nucleotide exchanges did not change the coding sequence, indicating that KCNJ6/KCNJ3 heteromeric receptor does not play a crucial role in JME pathophysiology (Hallmann et al., 2000). In addition, patients with Down syndrome (DS) may show infantile spasms (IS), the most frequent type of childhood epilepsy (Arya et al., 2011).…”

Section: Insights Into the Role Of Kir3x In Epilepsymentioning

confidence: 99%

Envisioning the role of inwardly rectifying potassium (Kir) channel in epilepsy

Akyüz

Köklü

Uner

et al. 2021

J of Neuroscience Research

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Epilepsy is a neurological disease characterized by two spontaneous seizures occurring within 24 hr, or two spontaneous seizures within 10 years after an unprovoked seizure (Fisher et al., 2014). The disease occurs by an increased tendency to generate seizures attributed to abnormal brain activity, caused by the disruption of the dynamic excitatory and inhibitory neuronal balance in the central nervous system (CNS) (Navidhamidi et al., 2017). Aberrant connectivity between neuronal networks may result in pathologically synchronized discharges and subsequently recurrent seizures (Aronica & Muhlebner, 2017). Epilepsy not only poses a significant burden on the patients and their families, but is also associated with significant social, behavioral, and economic effects (Tatum et al., 2009).Epilepsy affects people of all ages and has emerged as a global health concern affecting more than 70 million patients worldwide.Despite the recent advances in pre-clinical and clinical research, the

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Mutation analysis of the inwardly rectifying K+ channels KCNJ6 (GIRK2) and KCNJ3 (GIRK1) in juvenile myoclonic epilepsy

Cited by 14 publications

References 39 publications

Characterization of PTZ-Induced Seizure Susceptibility in a Down Syndrome Mouse Model That Overexpresses CSTB

Characterization of PTZ-Induced Seizure Susceptibility in a Down Syndrome Mouse Model That Overexpresses CSTB

A KCNJ6 gene polymorphism modulates theta oscillations during reward processing

Envisioning the role of inwardly rectifying potassium (Kir) channel in epilepsy

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