CTNNB1 Knockout in Inhibitory Neurons Contributes to Autism-Associated Behaviors in Mice

Open Access
Jiang, Joanna
Area of Honors:
Bachelor of Science
Document Type:
Thesis Supervisors:
  • Dr. Yingwei Mao, Thesis Supervisor
  • Dr. Gong Chen, Honors Advisor
  • Autism
  • Behavior
  • Brain
  • Genetics
  • CTNNB1
  • Parvalbumin
  • Inhibitory
  • ASD
Autism spectrum disorder (ASD) is an increasingly common condition for which there is currently no effective treatment. In order to begin developing targeted therapies, it is important to identify the causes and molecular mechanisms of autism. Previous studies have linked loss-of-function mutations of the CTNNB1 gene with the development of intellectual disability and ASD in children. The CTNNB1 gene is a key regulator of the canonical Wnt pathway, which plays an important role in neuronal and brain development. However, little is known about the function of CTNNB1 in specific neuronal subtypes. We examined the link between gene mutation and autism by generating a mouse model in which CTNNB1 was selectively knocked out in inhibitory parvalbumin (PV) interneurons. Behavior tests revealed that knockout mice had impaired social interaction and object recognition, increased repetitive behaviors, increased anxiety, and enhanced spatial memory compared to control littermates with normal expression of the gene. Knockout mice also showed decreased neuronal activity in the cortex as well as an increase in the number of PV interneurons. This suggests that mutation of CTNNB1 in inhibitory circuitry may directly cause several core symptoms of autism. We hope these findings can contribute to our overall understanding of the Wnt pathway and inhibitory circuitry, and ultimately be applied to the development of therapies for patients with autism.