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von Mücke-Heim, I.A.* ; Oldekamp, J.* ; Metzger, M.W.* ; Kläffgen, S.* ; Tang, H.* ; Walser, S.M.* ; Dedic, N.* ; Rammes, G.* ; Holsboer, F.* ; Wurst, W. ; Deussing, J.M.*

Establishment and behavioural characterization of a novel constitutive P2X7 receptor knockout mouse line.

Purinergic Signal., DOI: 10.1007/s11302-025-10074-x (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
The P2X7 receptor is an adenosine triphosphate (ATP)-gated ion channel expressed in different cell types of the brain. Polymorphisms in the P2RX7 gene have repeatedly been associated with psychiatric disorders including major depression. Depression is a stress-related disorder in which a dysregulation of the immune system has attracted increasing attention as a potential disease mechanism. The well-documented role of P2X7 in inflammatory conditions advocates its involvement in immune system dysregulation and depression genesis. However, understanding its exact role requires further research using appropriate animal models. Unfortunately, some of the most widely used P2X7 knockout mouse models are limited in their utility by the continuous expression of certain P2rx7 splice variants or even activation of de novo transcripts. To overcome this limitation, we generated a novel constitutive and complete P2X7 KO mouse line. These KO mice lack all known murine splice variants and protein expression resulting in a loss-of-function as confirmed by calcium imaging and by the inability of P2X7-deficient peritoneal macrophages to mount an appropriate interleukin (IL)-1β response. Comprehensive characterization using a battery of tests assessing locomotion, anxiety- and depression-related as well as social behaviour revealed differences in locomotor and exploratory behaviours. P2X7 KO mice showed slightly increased locomotor activity and reduced anxiety-related behaviour at baseline. Under conditions of chronic stress exposure, genotype-dependent differences largely dissolved while P2X7 deficiency promoted enhanced stress resilience with regard to social behaviour. Taken together, our findings add further evidence for an involvement of the P2X7 in shaping different behavioural responses and their modulation by stressful environments. This novel loss-of-function model will contribute to a better understanding of P2X7 in stress-associated behaviours in basic and translational neuropsychiatric research.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Behaviour ; Knockout Mice ; P2x7 Receptor ; P2rx7 Gene ; Purinergic; Gene-expression; Cutting Edge; Cells; P2rx7; Mice; Inflammasome; Mechanisms; Depression; Adenosine; Diseases
ISSN (print) / ISBN 1573-9538
e-ISSN 1573-9546
Zeitschrift Purinergic Signalling
Verlag Springer
Verlagsort Dordrecht
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Förderungen International Max Planck Research School for Translational Psychiatry (IMPRS-TP)
Else-Kroener-Fresenius Foundation
German Federal Ministry of Education and Research
Marie Sklodowska-Curie innovative training network PurinesDX
Projekt DEAL