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Metzger, M.W.* ; Walser, S.M.* ; Dedic, N.* ; Aprile-Garcia, F.* ; Jakubcakova, V.* ; Adamczyk, M.* ; Webb, K.J.* ; Uhr, M.* ; Refojo, D.* ; Schmidt, M.V.* ; Friess, E.* ; Steiger, A.* ; Kimura, M.* ; Chen, A.* ; Holsboer, F.* ; Arzt, E.* ; Wurst, W. ; Deussing, J.M.*

Heterozygosity for the mood disorder-associated variant Gln460Arg alters P2X7 receptor function and sleep quality.

J. Neurosci. 37, 11688-11700 (2017)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
A single nucleotide polymorphism substitution from glutamine (Gln, Q) to arginine (Arg, R) at codon 460 of the purinergic P2X7 receptor (P2X7R) has repeatedly been associated with mood disorders. The P2X7R-Gln460Arg variant per se is not compromised in its function. However, heterologous expression of P2X7R-Gln460Arg together with wild-type P2X7R has recently been demonstrated to impair receptor function. Here we show that this also applies to humanized mice coexpressing both human P2X7R variants. Primary hippocampal cells derived from heterozygous mice showed an attenuated calcium uptake upon agonist stimulation. While humanized mice were unaffected in their behavioral repertoire under basal housing conditions, mice that harbor both P2X7R variants showed alterations in their sleep quality resembling signs of a prodromal disease stage. Also healthy heterozygous human subjects showed mild changes in sleep parameters. These results indicate that heterozygosity for the wild-type P2X7R and its mood disorder-associated variant P2X7R-Gln460Arg represents a genetic risk factor, which is potentially able to convey susceptibility to mood disorders.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Humanized Mouse Model ; Mood Disorder ; P2x7 Receptor ; Purinergic Signaling ; Sleep ; Stress; Major Depressive Disorder; Social Defeat Stress; P2rx7 Gene; P2x(7) Receptors; Neuropsychiatric Disorders; Spindle Activity; Knockout Mice; Animal-models; Atp; Polymorphism
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 0270-6474
e-ISSN 1529-2401
Zeitschrift Journal of Neuroscience
Quellenangaben Band: 37, Heft: 48, Seiten: 11688-11700 Artikelnummer: , Supplement: ,
Verlag Society for Neuroscience
Verlagsort Washington
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
POF Topic(s) 30204 - Cell Programming and Repair
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500500-001
DOI 10.1523/JNEUROSCI.3487-16.2017
WOS ID WOS:000417372300015
Scopus ID 85036568063
PubMed ID 29079688
Erfassungsdatum 2017-12-28
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