Genetic mutations in mouse models for the comorbidity of autism spectrum disorders and epilepsy: A systematic review

The complex relationship between autism spectrum disorders (ASD) and epilepsy is yet to be well established. The increased prevalence of epilepsy in ASD and vice versa has resulted in each disorder being considered a “comorbidity” of the other. Their common co-occurrence has been suggestive of certain shared neurobiological mechanisms or pathways. Specifically, the discovery of novel genetic mutations in the comorbidity has pointed to abnormalities in synaptic formation and function, which alter the balance between normal neuronal excitation and inhibition. Animal models in general, and mouse models using knockout, knock-in, or CRISPR-Cas9 technology, can be informative in sorting out the relationship in the comorbidity and gaining insights into its medical and behavioral complexities. As a result of the growing mechanistic information on the comorbidity, we can expect the development of genetic mutation and pathway-specific targeted treatments. A coordinated global effort between researchers on epilepsy and ASD is crucial, including conducting timely systematic reviews and meta-analyses on animal models. This study aimed to review the genetic mutations commonly used to develop mouse models for the comorbidity of ASD and epilepsy.