Cognitive impairment and autistic-like behaviour in SAPAP4-deficient mice
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 Woehr, Markus Voerckel, Karl J. Calzada-Wack, Julia Fuchs, Helmut Gailus-Durner, Valerie de Angelis, Martin Hrabe Garner, Craig C. Kreienkamp, Hans-Juergen Kindler, Stefan |
Stichwörter: | COMMUNICATION; DELETION; HIPPOCAMPAL; KNOCKOUT MOUSE MODEL; LOCALIZATION; MUTATIONS; OBSESSIVE-COMPULSIVE DISORDER; PROTEINS; Psychiatry; SYNAPTIC PLASTICITY; VARIANTS | Erscheinungsdatum: | 2019 | Herausgeber: | SPRINGERNATURE | Journal: | TRANSLATIONAL PSYCHIATRY | Volumen: | 9 | 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. |
ISSN: | 21583188 | DOI: | 10.1038/s41398-018-0327-z |
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geprüft am 20.05.2024