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dc.contributor.authorSteubler, Vicky
dc.contributor.authorErdinger, Susanne
dc.contributor.authorBack, Michaela K
dc.contributor.authorLudewig, Susann
dc.contributor.authorFässler, Dominique
dc.contributor.authorRichter, Max
dc.contributor.authorHan, Kang
dc.contributor.authorSlomianka, Lutz
dc.contributor.authorAmrein, Irmgard
dc.contributor.authorvon Engelhardt, Jakob
dc.contributor.authorWolfer, David P
dc.contributor.authorKorte, Martin
dc.contributor.authorMüller, Ulrike C
dc.date.accessioned2021-09-28T15:06:14Z
dc.date.available2021-09-28T15:06:14Z
dc.date.issued2021-05-19
dc.identifier.citationEMBO J. 2021 Jun 15;40(12):e107471. doi: 10.15252/embj.2020107471. Epub 2021 May 19.en_US
dc.identifier.pmid34008862
dc.identifier.doi10.15252/embj.2020107471
dc.identifier.urihttp://hdl.handle.net/10033/623051
dc.description.abstractThe key role of APP for Alzheimer pathogenesis is well established. However, perinatal lethality of germline knockout mice lacking the entire APP family has so far precluded the analysis of its physiological functions for the developing and adult brain. Here, we generated conditional APP/APLP1/APLP2 triple KO (cTKO) mice lacking the APP family in excitatory forebrain neurons from embryonic day 11.5 onwards. NexCre cTKO mice showed altered brain morphology with agenesis of the corpus callosum and disrupted hippocampal lamination. Further, NexCre cTKOs revealed reduced basal synaptic transmission and drastically reduced long-term potentiation that was associated with reduced dendritic length and reduced spine density of pyramidal cells. With regard to behavior, lack of the APP family leads not only to severe impairments in a panel of tests for learning and memory, but also to an autism-like phenotype including repetitive rearing and climbing, impaired social communication, and deficits in social interaction. Together, our study identifies essential functions of the APP family during development, for normal hippocampal function and circuits important for learning and social behavior.en_US
dc.language.isoenen_US
dc.publisherWiley/EMBO Pressen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAlzheimeren_US
dc.subjectAmyloid precursor proteinen_US
dc.subjectAutism spectrum disorderen_US
dc.subjectlearning and memoryen_US
dc.subjectsynaptic plasticityen_US
dc.titleLoss of all three APP family members during development impairs synaptic function and plasticity, disrupts learning, and causes an autism-like phenotype.en_US
dc.typeArticleen_US
dc.identifier.eissn1460-2075
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalThe EMBO journalen_US
dc.source.volume40
dc.source.issue12
dc.source.beginpagee107471
dc.source.endpage
refterms.dateFOA2021-09-28T15:06:14Z
dc.source.journaltitleThe EMBO journal
dc.source.countryEngland


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International