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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)
Publ. Version/Full Text DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 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
ISSN (print) / ISBN 0270-6474
e-ISSN 1529-2401
Journal Journal of Neuroscience
Quellenangaben Volume: 37, Issue: 48, Pages: 11688-11700 Article Number: , Supplement: ,
Publisher Society for Neuroscience
Publishing Place Washington
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)