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- W2000584367 abstract "High-affinity nicotinic receptors containing β2 subunits (β2*) are widely expressed in the brain, modulating many neuronal processes and contributing to neuropathologies such as Alzheimer's disease, Parkinson's disease and epilepsy. Mutations in both the α4 and β2 subunits are associated with a rare partial epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In this study, we introduced one such human missense mutation into the mouse genome to generate a knock-in strain carrying a valine-to-leucine mutation β2V287L. β2V287L mice were viable and born at an expected Mendelian ratio. Surprisingly, mice did not show an overt seizure phenotype; however, homozygous mice did show significant alterations in their activity–rest patterns. This was manifest as an increase in activity during the light cycle suggestive of disturbances in the normal sleep patterns of mice; a parallel phenotype to that found in human ADNFLE patients. Consistent with the role of nicotinic receptors in reward pathways, we found that β2V287L mice did not develop a normal proclivity to voluntary wheel running, a model for natural reward. Anxiety-related behaviors were also affected by the V287L mutation. Mutant mice spent more time in the open arms on the elevated plus maze suggesting that they had reduced levels of anxiety. Together, these findings emphasize several important roles of β2* nicotinic receptors in complex biological processes including the activity–rest cycle, natural reward and anxiety." @default.
- W2000584367 created "2016-06-24" @default.
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- W2000584367 date "2010-07-06" @default.
- W2000584367 modified "2023-10-16" @default.
- W2000584367 title "Altered activity–rest patterns in mice with a human autosomal-dominant nocturnal frontal lobe epilepsy mutation in the β2 nicotinic receptor" @default.
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- W2000584367 doi "https://doi.org/10.1038/mp.2010.78" @default.
- W2000584367 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2970689" @default.
- W2000584367 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20603624" @default.
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