TY - JOUR
T1 - KMT2C knockout generates ASD-like behaviors in mice
AU - Brauer, Bastian
AU - Merino-Veliz, Nicolas
AU - Ahumada-Marchant, Constanza
AU - Arriagada, Gloria
AU - Bustos, Fernando J.
N1 - Publisher Copyright:
Copyright © 2023 Brauer, Merino-Veliz, Ahumada-Marchant, Arriagada and Bustos.
PY - 2023
Y1 - 2023
N2 - Neurodevelopmental disorders have been associated with genetic mutations that affect cellular function, including chromatin regulation and epigenetic modifications. Recent studies in humans have identified mutations in KMT2C, an enzyme responsible for modifying histone tails and depositing H3K4me1 and H3K4me3, as being associated with Kleefstra syndrome 2 and autism spectrum disorder (ASD). However, the precise role of KMT2C mutations in brain disorders remains poorly understood. Here we employed CRISPR/Cas9 gene editing to analyze the effects of KMT2C brain specific knockout on animal behavior. Knocking out KMT2C expression in cortical neurons and the mouse brain resulted in decreased KMT2C levels. Importantly, KMT2C brain specific knockout animals exhibited repetitive behaviors, social deficits, and intellectual disability resembling ASD. Our findings shed light on the involvement of KMT2C in neurodevelopmental processes and establish a valuable model for elucidating the cellular and molecular mechanisms underlying KMT2C mutations and their relationship to Kleefstra syndrome 2 and ASD.
AB - Neurodevelopmental disorders have been associated with genetic mutations that affect cellular function, including chromatin regulation and epigenetic modifications. Recent studies in humans have identified mutations in KMT2C, an enzyme responsible for modifying histone tails and depositing H3K4me1 and H3K4me3, as being associated with Kleefstra syndrome 2 and autism spectrum disorder (ASD). However, the precise role of KMT2C mutations in brain disorders remains poorly understood. Here we employed CRISPR/Cas9 gene editing to analyze the effects of KMT2C brain specific knockout on animal behavior. Knocking out KMT2C expression in cortical neurons and the mouse brain resulted in decreased KMT2C levels. Importantly, KMT2C brain specific knockout animals exhibited repetitive behaviors, social deficits, and intellectual disability resembling ASD. Our findings shed light on the involvement of KMT2C in neurodevelopmental processes and establish a valuable model for elucidating the cellular and molecular mechanisms underlying KMT2C mutations and their relationship to Kleefstra syndrome 2 and ASD.
KW - ASD
KW - behavior
KW - CRISPR/Cas9
KW - epigenetics
KW - KMT2C
UR - http://www.scopus.com/inward/record.url?scp=85166432983&partnerID=8YFLogxK
U2 - 10.3389/fcell.2023.1227723
DO - 10.3389/fcell.2023.1227723
M3 - Article
AN - SCOPUS:85166432983
SN - 2296-634X
VL - 11
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 1227723
ER -