Elevated expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in cerebellar unipolar brush cells of a Down syndrome mouse model.
- Authors
- Harashima, Chie; Jacobowitz, David M; Stoffel, Markus; Chakrabarti, Lina; Haydar, Tarik F; Siarey, Richard J; Galdzicki, Zygmunt
- Year
- 2006
- Journal
- Cellular and molecular neurobiology
- PMID
- 16783527
- DOI
- 10.1007/s10571-006-9066-4
- PMCID
- PMC11520672
1. Down syndrome (DS) arises from the presence of three copies of chromosome (Chr.) 21. Fine motor learning deficits found in DS from childhood to adulthood result from expression of extra genes on Chr. 21, however, it remains unclear which if any of these genes are the specific causes of the cognitive and motor dysfunction. DS cerebellum displays morphological abnormalities that likely contribute to the DS motor phenotype. 2. The G-protein-activated inwardly rectifying potassium channel subunit 2 (GIRK2) is expressed in cerebellum and can shunt dendritic conductance and attenuate postsynaptic potentials. We have used an interbreeding approach to cross a genetic mouse model of DS (Ts65Dn) with Girk2 knockout mice and examined its relative expression level by quantitative real-time RT-PCR, Western blotting and immunohistochemistry. 3. We report here for the first time that GIRK2 is expressed in unipolar brush cells, which are excitatory interneurons of the vestibulocerebellum and dorsal cochlear nucleus. Analysis of disomic-Ts65Dn/Girk2((+/+/-)) and heterozygous-Diploid/Girk2((+/-)) mice shows that GIRK2 expression in Ts65Dn lobule X follows gene dosage. The lobule X of Ts65Dn mice contain greater numbers of unipolar brush cells co-expressing GIRK2 and calretinin than the control mouse groups. 4. These results demonstrate that gene triplication can impact specific cell types in the cerebellum. We hypothesize that GIRK2 overexpression will adversely affect cerebellar circuitry in Ts65Dn vestibulocerebellum and dorsal cochlear nucleus due to GIRK2 shunting properties and its effects on resting membrane potential.
No figures extracted from this document.
No chunks — full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
No citations found.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| A KCNJ6 gene polymorphism modulates theta oscillations during reward processing. | 2017 | 27993610 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Altered synaptic functions in a humanized mouse model of down syndrome (TcMAC21): Implications for seizure susceptibility. | Shao LR et al. | — | 2025 | → |
| Differential Modulation of Cerebellar Flocculus Unipolar Brush Cells during Vestibular Compensation. | Liu D et al. | — | 2023 | → |
| Glutamatergic synaptic deficits in the prefrontal cortex of the Ts65Dn mouse model for Down syndrome | Thomazeau A et al. | — | 2023 | — |
| Glutamatergic synaptic deficits in the prefrontal cortex of the Ts65Dn mouse model for Down syndrome. | Thomazeau A et al. | — | 2023 | → |
| Increased propensity for infantile spasms and altered neocortical excitation-inhibition balance in a mouse model of down syndrome carrying human chromosome 21. | Shao LR et al. | — | 2023 | → |
| Enhanced GIRK2 channel signaling in Down syndrome: A feasible role in the development of abnormal nascent neural circuits. | Kleschevnikov AM | — | 2022 | → |
| GABA<sub>B</sub> Receptors and Cognitive Processing in Health and Disease. | Vlachou S | — | 2022 | → |
| GIRK2 Channels in Down Syndrome and Alzheimer's Disease. | Kleschevnikov A | — | 2022 | → |
| Rethinking Intellectual Disability from Neuro- to Astro-Pathology. | Fernández-Blanco Á et al. | — | 2020 | → |
| Neuronal and vascular deficits following chronic adaptation to high altitude. | Cramer NP et al. | — | 2019 | → |
| GABAergic over-inhibition, a promising hypothesis for cognitive deficits in Down syndrome. | Zorrilla de San Martin J et al. | — | 2018 | → |
| Proteomic analysis of six- and twelve-month hippocampus and cerebellum in a murine Down syndrome model. | Vacano GN et al. | — | 2018 | → |
| A KCNJ6 gene polymorphism modulates theta oscillations during reward processing. | Kamarajan C et al. | — | 2017 | → |
| Altered intrinsic and network properties of neocortical neurons in the Ts65Dn mouse model of Down syndrome. | Cramer NP et al. | — | 2015 | → |
| GIRK Channels: A Potential Link Between Learning and Addiction. | Tipps ME et al. | — | 2015 | → |
| Human chromosome 21 orthologous region on mouse chromosome 17 is a major determinant of Down syndrome-related developmental cognitive deficits. | Zhang L et al. | — | 2014 | → |
| Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down's syndrome. | Szemes M et al. | — | 2013 | → |
| Down syndrome: the brain in trisomic mode. | Dierssen M | — | 2012 | → |
| Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome. | Best TK et al. | — | 2012 | → |
| Electrophysiological, morphological, and topological properties of two histochemically distinct subpopulations of cerebellar unipolar brush cells. | Kim JA et al. | — | 2012 | → |
| Increased excitability and altered action potential waveform in cerebellar granule neurons of the Ts65Dn mouse model of Down syndrome. | Usowicz MM et al. | — | 2012 | → |
| Lack of behavioral and cognitive effects of chronic ethosuximide and gabapentin treatment in the Ts65Dn mouse model of Down syndrome. | Vidal V et al. | — | 2012 | → |
| Molecular and cellular alterations in Down syndrome: toward the identification of targets for therapeutics. | Créau N | — | 2012 | → |
| Synaptic pathology of Down syndrome. | Garner CC et al. | — | 2012 | → |
| Trisomy of the G protein-coupled K+ channel gene, Kcnj6, affects reward mechanisms, cognitive functions, and synaptic plasticity in mice. | Cooper A et al. | — | 2012 | → |
| The unipolar brush cell: a remarkable neuron finally receiving deserved attention. | Mugnaini E et al. | — | 2011 | → |
| GABAB-GIRK2-mediated signaling in Down syndrome. | Cramer NP et al. | — | 2010 | → |
| Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. | Baek KH et al. | — | 2009 | → |
| Functional genomic analysis of amniotic fluid cell-free mRNA suggests that oxidative stress is significant in Down syndrome fetuses. | Slonim DK et al. | — | 2009 | → |
| Gene expression signature of cerebellar hypoplasia in a mouse model of Down syndrome during postnatal development. | Laffaire J et al. | — | 2009 | → |
| Dynamic metabotropic control of intrinsic firing in cerebellar unipolar brush cells. | Russo MJ et al. | — | 2008 | → |
| Down syndrome gene dosage imbalance on cerebellum development. | Moldrich RX et al. | — | 2007 | → |
| Intrinsic properties and mechanisms of spontaneous firing in mouse cerebellar unipolar brush cells. | Russo MJ et al. | — | 2007 | → |
| Mental retardation in Down syndrome: from gene dosage imbalance to molecular and cellular mechanisms. | Rachidi M et al. | — | 2007 | → |
| Synaptic and cognitive abnormalities in mouse models of Down syndrome: exploring genotype-phenotype relationships. | Belichenko PV et al. | — | 2007 | → |