WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice.

Scientists studied mice with changes to a gene called WDR62, which has been linked to autism. They found that mice missing this gene showed autism-like behaviors including social difficulties and repetitive actions. Interestingly, even when brain size stayed normal, the mice still had these autism behaviors. The researchers also found that a treatment called retinoic acid helped reduce the autism-like behaviors in the mice.

This mouse study investigated the role of WDR62 gene mutations in autism spectrum disorder (ASD). Researchers found that complete WDR62 knockout caused reduced brain size, learning/memory impairments, and ASD-like behaviors. Importantly, mice with WDR62 depletion only in mature neurons showed normal brain size but still displayed social interaction difficulties and repetitive behaviors. The study revealed that WDR62 regulates dendritic spine formation and excitatory synaptic transmission in brain neurons.

Treatment with retinoic acid significantly improved ASD-like behaviors in mice with partial WDR62 deficiency, potentially by restoring expression of ASD and synapse-related genes. These findings suggest WDR62's role in autism may be independent of its effects on brain size.

Provides preliminary evidence for WDR62 as an autism risk gene and suggests potential therapeutic targets. However, findings are from animal models and require human validation. Retinoic acid shows promise but needs extensive safety testing before clinical consideration.

Animal model findings may not directly translate to humans. Sample sizes not reported. Single study requires replication. Retinoic acid intervention needs safety and efficacy testing in humans before clinical consideration.

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.