Healthcare (Commonwealth Union) – The condition autism spectrum disorder (ASD) is a neurodevelopmental disorder that has an impact on communication, behavior, and social engagements. It is called a “spectrum” disorder due to its inclusion of a wide range of symptoms and levels of disability, from mild to severe.
Previously believed to be distinct disorders, ASD encompasses childhood disintegrative disorder, Asperger’s syndrome, autism, and an unspecified general developmental disability.
ASD usually begins in the early years of an individual’s life, and as it progresses, social engagements may become challenging. Diagnosing ASD and treating it in early years is known to improve life for individuals with the condition.
To investigate the genetic roots of ASD, researchers at Kobe University have developed a collection of 63 mouse embryonic stem cell lines, each carrying mutations strongly linked to the condition. A newly developed, highly efficient method for editing the genomes of embryonic stem cells made this breakthrough possible.
It is widely accepted that genetics plays a key role in ASD, but the problem is that the exact mechanisms and causes remain unclear. Researchers from the Salk Institute a few years back explored how gene expression may bring about altered brain development in individuals with ASD, which indicates the significance of the role of genes in ASD.
To explore the biological foundations of complex disorders like autism, scientists rely on models: cell models help reveal how specific gene mutations affect cell structure and function, while animal models demonstrate how these genetic changes impact overall health and behavior. Despite the biological differences between mice and humans, many genes involved in disease are remarkably similar, often producing comparable effects in both species.
“One of the problems, however, is the lack of a standardized biological model to study the effects of the different mutations associated with autism spectrum disorder. This makes it difficult to find out, for example, whether they have common effects or what is specific to certain cell types,” said Takumi Toru a neuroscientist at Kobe University.
Twelve years ago, Takumi and his research group set out to tackle this challenge. With extensive experience in using mouse models to study the disorder, they merged a traditional technique for modifying mouse embryonic stem cells—which have the potential to transform into nearly any type of cell—with the then-recently introduced CRISPR gene-editing technology. CRISPR offered a precise, user-friendly way to alter genes, and this combination proved remarkably effective. It enabled the team at Kobe University to create a collection of 63 distinct mouse embryonic stem cell lines, each carrying one of the genetic mutations most strongly linked to autism spectrum disorder.
In a recent publication in Cell Genomics, Takumi’s team reported that they successfully developed these modified cells into a wide variety of cell types and tissues—even generating adult mice that carried the same genetic mutations. The mere ability to do this confirmed the value of the cell lines as reliable models for investigating autism. Moreover, these cell lines made it possible to conduct comprehensive data analyses that pinpointed specific genes with abnormal activity and identified the exact cell types where these irregularities occurred.
Among the most striking findings from this analysis was the discovery that mutations associated with autism frequently disrupt neurons’ ability to clear out malformed proteins. According to Takumi this is particularly noteworthy as neurons have the unusual ability to produce proteins locally, and if this protein quality control fails, it could be a key contributor to neuronal dysfunction.
The neuroscientist from Kobe University believes his team’s accomplishment—now accessible to other researchers and adaptable to various lab methods and genetic targets—will serve as a vital tool for the scientific community working to understand autism and develop potential drug therapies.
“Interestingly, the genetic variants we studied are also implicated in other neuropsychiatric disorders such as schizophrenia and bipolar disorder. So, this library may be useful for studying other conditions as well.”
