Impact of KDM6B mosaic brain knockout on synaptic function and behavior
| dc.contributor.author | Nardocci, Gino | |
| dc.date.accessioned | 2025-01-22T18:27:12Z | |
| dc.date.available | 2025-01-22T18:27:12Z | |
| dc.date.issued | 2024-12 | |
| dc.description.abstract | Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social communication, repetitive behaviors, and restricted interests. Epigenetic modifications serve as critical regulators of gene expression playing a crucial role in controlling brain function and behavior. Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, has emerged as one of the highest ASD risk genes, but the precise effects of KDM6B mutations on neuronal activity and behavioral function remain elusive. Here we show the impact of KDM6B mosaic brain knockout on the manifestation of different autistic-like phenotypes including repetitive behaviors, social interaction, and significant cognitive deficits. Moreover, KDM6B mosaic knockout display abnormalities in hippocampal excitatory synaptic transmission decreasing NMDA receptor mediated synaptic transmission and plasticity. Understanding the intricate interplay between epigenetic modifications and neuronal function may provide novel insights into the pathophysiology of ASD and potentially inform the development of targeted therapeutic interventions. | |
| dc.description.sponsorship | This work was supported by: ANID Fondecyt Iniciacion 11180540 (FJB), ANID PAI 77180077 (FJB), Exploraci\u00F3n-ANID 13220203 (FJB), ANID-MILENIO (NCN2023_32, FJB, LVN), UNAB DI-02-22/REG (FJB), Fondequip EQM230028 (FJB), UNAB DI-06-24/REG (FJB), ANID-FONDECYT 1220480 (GA), ANID-FONDECYT 1201848 (A.E.C), ANID-FONDECYT 1230454 (LVN), DI-03-21/APP UNAB (BB), Fondequip EQM160154 (A.E.C) and by ANID Millennium Science Initiative Program (P09-022F to A.E.C). R.C.M was supported by ANID-FONDECYT postdoctorado grant #3190793. CA-G and NM-V were supported by PhD fellowship from ANID #21201603 (to CA-G) and #21211967 (to NM-V). | |
| dc.identifier.doi | 10.1038/s41598-024-70728-5 | |
| dc.identifier.issn | 20452322 | |
| dc.identifier.uri | http://repositorio.uandes.cl/handle/uandes/982 | |
| dc.language.iso | en_US | |
| dc.publisher | Scientific Reports | |
| dc.subject | ASD | |
| dc.subject | Behavior | |
| dc.subject | Gene Editing | |
| dc.subject | KDM6B | |
| dc.subject | NMDA | |
| dc.title | Impact of KDM6B mosaic brain knockout on synaptic function and behavior | |
| dc.type | Article |