WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice / 神经科学通报·英文版
Neuroscience Bulletin
;
(6): 1333-1347, 2023.
Artículo
en Inglés
| WPRIM
| ID: wpr-1010605
ABSTRACT
Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Trastorno Autístico
/
Encéfalo
/
Ratones Noqueados
/
Proteínas de Ciclo Celular
/
Trastorno del Espectro Autista
/
Microcefalia
/
Proteínas del Tejido Nervioso
Límite:
Animales
Idioma:
Inglés
Revista:
Neuroscience Bulletin
Año:
2023
Tipo del documento:
Artículo
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