Cover Image

Loss of all three APP family members during development impairs synaptic function and plasticity, disrupts learning, and causes an autism-like phenotype

The 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...

Full description

Saved in:
Bibliographic Details
Main Authors: Steubler, Vicky (Author) , Erdinger, Susanne (Author) , Back, Michaela K (Author) , Ludewig, Susann (Author) , Fäßler, Dominique (Author) , Richter, Max (Author) , Han, Kang (Author) , Slomianka, Lutz (Author) , Amrein, Irmgard (Author) , Engelhardt, Jakob von (Author) , Wolfer, David Paul (Author) , Korte, Martin (Author) , Müller, Ulrike C. (Author)
Format: Article (Journal)
Language:English
Published: 19 May 2021
In: The EMBO journal
Year: 2021, Volume: 40, Issue: 12, Pages: 1-23
ISSN:1460-2075
DOI:10.15252/embj.2020107471
Online Access:Resolving-System, kostenfrei, Volltext: https://doi.org/10.15252/embj.2020107471
Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.15252/embj.2020107471
Get full text
Author Notes:Vicky Steubler, Susanne Erdinger, Michaela K Back, Susann Ludewig, Dominique Fässler, Max Richter, Kang Han, Lutz Slomianka, Irmgard Amrein, Jakob von Engelhardt, David P Wolfer, Martin Korte & Ulrike C Müller
Description
Summary:The 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.
Item Description:Gesehen am 21.05.2021
Physical Description:Online Resource
ISSN:1460-2075
DOI:10.15252/embj.2020107471

Similar Items