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@ARTICLE{vonMckeHeim:281868,
      author       = {von Mücke-Heim, Iven-Alex and Oldekamp, Judit and Metzger,
                      Michael W and Kläffgen, Sarah and Tang, Hao and Walser,
                      Sandra M and Dedic, Nina and Rammes, Gerhard and Holsboer,
                      Florian and Wurst, Wolfgang and Deussing, Jan M},
      title        = {{E}stablishment and behavioural characterization of a novel
                      constitutive {P}2{X}7 receptor knockout mouse line.},
      journal      = {Purinergic signalling},
      volume       = {21},
      number       = {5},
      issn         = {1573-9538},
      address      = {Dordrecht},
      publisher    = {Springer Science + Business Media B.V.},
      reportid     = {DZNE-2025-01239},
      pages        = {1077 - 1092},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Animals / Receptors, Purinergic P2X7: genetics / Receptors,
                      Purinergic P2X7: metabolism / Mice, Knockout / Mice /
                      Behavior, Animal: physiology / Male / Mice, Inbred C57BL /
                      Depression: genetics / Depression: metabolism / Anxiety:
                      genetics / Anxiety: metabolism / Disease Models, Animal /
                      Stress, Psychological: metabolism / Behaviour (Other) /
                      Knockout mice (Other) / P2X7 receptor (Other) / P2rx7 gene
                      (Other) / Purinergic (Other) / Receptors, Purinergic P2X7
                      (NLM Chemicals) / P2rx7 protein, mouse (NLM Chemicals)},
      cin          = {AG Wurst},
      ddc          = {540},
      cid          = {I:(DE-2719)1140001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40024982},
      pmc          = {pmc:PMC12595207},
      doi          = {10.1007/s11302-025-10074-x},
      url          = {https://pub.dzne.de/record/281868},
}