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@ARTICLE{Trossbach:280994,
      author       = {Trossbach, S. V. and Bader, V. and Hecher, L. and Pum, M.
                      E. and Masoud, S. T. and Prikulis, I. and Schäble, S. and
                      de Souza Silva, M. A. and Su, P. and Boulat, B. and
                      Chwiesko, C. and Poschmann, G. and Stühler, K. and Lohr, K.
                      M. and Stout, K. A. and Oskamp, A. and Godsave, S. F. and
                      Müller-Schiffmann, A. and Bilzer, T. and Steiner, H. and
                      Peters, P. J. and Bauer, Andreas and Sauvage, M. and Ramsey,
                      A. J. and Miller, G. W. and Liu, F. and Seeman, P. and
                      Brandon, N. J. and Huston, J. P. and Korth, C.},
      title        = {{M}isassembly of full-length {D}isrupted-in-{S}chizophrenia
                      1 protein is linked to altered dopamine homeostasis and
                      behavioral deficits},
      journal      = {Molecular psychiatry},
      volume       = {21},
      issn         = {1476-5578},
      address      = {London},
      publisher    = {Macmillan},
      reportid     = {FZJ-2016-00705},
      pages        = {1561–1572},
      year         = {2016},
      abstract     = {Disrupted-in-schizophrenia 1 (DISC1) is a mental illness
                      gene first identified in a Scottish pedigree. So far,
                      DISC1-dependent phenotypes in animal models have been
                      confined to expressing mutant DISC1. Here we investigated
                      how pathology of full-length DISC1 protein could be a major
                      mechanism in sporadic mental illness. We demonstrate that a
                      novel transgenic rat model, modestly overexpressing the
                      full-length DISC1 transgene, showed phenotypes consistent
                      with a significant role of DISC1 misassembly in mental
                      illness. The tgDISC1 rat displayed mainly perinuclear DISC1
                      aggregates in neurons. Furthermore, the tgDISC1 rat showed a
                      robust signature of behavioral phenotypes that includes
                      amphetamine supersensitivity, hyperexploratory behavior and
                      rotarod deficits, all pointing to changes in dopamine (DA)
                      neurotransmission. To understand the etiology of the
                      behavioral deficits, we undertook a series of molecular
                      studies in the dorsal striatum of tgDISC1 rats. We observed
                      an $80\%$ increase in high-affinity DA D2 receptors, an
                      increased translocation of the dopamine transporter to the
                      plasma membrane and a corresponding increase in DA inflow as
                      observed by cyclic voltammetry. A reciprocal relationship
                      between DISC1 protein assembly and DA homeostasis was
                      corroborated by in vitro studies. Elevated cytosolic
                      dopamine caused an increase in DISC1 multimerization,
                      insolubility and complexing with the dopamine transporter,
                      suggesting a physiological mechanism linking DISC1 assembly
                      and dopamine homeostasis. DISC1 protein pathology and its
                      interaction with dopamine homeostasis is a novel cellular
                      mechanism that is relevant for behavioral control and may
                      have a role in mental illness.},
      cin          = {INM-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-2-20090406},
      pnm          = {571 - Connectivity and Activity (POF3-571)},
      pid          = {G:(DE-HGF)POF3-571},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000388719600011},
      pubmed       = {pmid:26754951},
      doi          = {10.1038/mp.2015.194},
      url          = {https://juser.fz-juelich.de/record/280994},
}