| Autor(en): | Schob, Claudia
Morellini, Fabio
Ohana, Ora
Bakota, Lidia
Hrynchak, Mariya V.
Brandt, Roland
Brockmann, Marco D.
Cichon, Nicole
Hartung, Henrike
Hanganu-Opatz, Ileana L.
Kraus, Vanessa
Scharf, Sarah
Herrmans-Borgmeyer, Irm
Schweizer, Michaela
Kuhl, Dietmar
Wöhr, Markus
Vörckel, Karl J.
Calzada-Wack, Julia
Fuchs, Helmut
Gailus-Durner, Valérie
Hrabě de Angelis, Martin
Garner, Craig C.
Kreienkamp, Hans-Jürgen
Kindler, Stefan |
Affiliationen: | Institute for Human Genetics, University Medical Centre Hamburg-Eppendorf, 20246, Hamburg, Germany.
Behavioral Biology, Centre for Molecular Neurobiology Hamburg (ZMNH), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Institute for Molecular and Cellular Cognition, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Neurobiology, University of Osnabrück, 49076, Osnabrück, Germany.
Department of Neurobiology, University of Osnabrück, 49076, Osnabrück, Germany.
Department of Neurobiology, University of Osnabrück, 49076, Osnabrück, Germany.
Developmental Neurophysiology, Department of Neuroanatomy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Developmental Neurophysiology, Department of Neuroanatomy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Developmental Neurophysiology, Department of Neuroanatomy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Developmental Neurophysiology, Department of Neuroanatomy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Behavioral Biology, Centre for Molecular Neurobiology Hamburg (ZMNH), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Behavioral Biology, Centre for Molecular Neurobiology Hamburg (ZMNH), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Transgenic Mouse Facility, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Morphology and Electron Microscopy, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute for Molecular and Cellular Cognition, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Behavioral Neuroscience, Experimental and Biological Psychology, Faculty of Psychology, Philipps-University of Marburg, 35032, Marburg, Germany.
Behavioral Neuroscience, Experimental and Biological Psychology, Faculty of Psychology, Philipps-University of Marburg, 35032, Marburg, Germany.
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Centre Munich, German Research Centre for Environmental Health, 85764, Neuherberg, Germany.
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Centre Munich, German Research Centre for Environmental Health, 85764, Neuherberg, Germany.
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Centre Munich, German Research Centre for Environmental Health, 85764, Neuherberg, Germany.
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Centre Munich, German Research Centre for Environmental Health, 85764, Neuherberg, Germany.
Chair of Experimental Genetics, School of Life Science Weihenstephan, Technische Universität München, 85354, Freising, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.
German Centre for Neurodegenerative Diseases (DZNE), c/o Charité University Medical Centre, 10117, Berlin, Germany.
Institute for Human Genetics, University Medical Centre Hamburg-Eppendorf, 20246, Hamburg, Germany.
Institute for Human Genetics, University Medical Centre Hamburg-Eppendorf, 20246, Hamburg, Germany. kindler@uke.de. |
Erscheinungsdatum: | 2019 |
Journal: | Translational psychiatry |
Volumen: | 9 |
Ausgabe: | 1 |
Startseite: | 7 |
Zusammenfassung: | In humans, genetic variants of DLGAP1-4 have been linked with neuropsychiatric conditions, including autism spectrum disorder (ASD). While these findings implicate the encoded postsynaptic proteins, SAPAP1-4, in the etiology of neuropsychiatric conditions, underlying neurobiological mechanisms are unknown. To assess the contribution of SAPAP4 to these disorders, we characterized SAPAP4-deficient mice. Our study reveals that the loss of SAPAP4 triggers profound behavioural abnormalities, including cognitive deficits combined with impaired vocal communication and social interaction, phenotypes reminiscent of ASD in humans. These behavioural alterations of SAPAP4-deficient mice are associated with dramatic changes in synapse morphology, function and plasticity, indicating that SAPAP4 is critical for the development of functional neuronal networks and that mutations in the corresponding human gene, DLGAP4, may cause deficits in social and cognitive functioning relevant to ASD-like neurodevelopmental disorders. |
DOI: | 10.1038/s41398-018-0327-z |
Externe URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341115 |
