The new research at the Children's Medical Center Research Institute (CRI) provides the new insight into the genetic basis of neuropsychiatric disorders. ARID1B gene was mutated in the mouse model and later used to show that growth hormone treatments reverse some manifestations of the mutation.
The ARID1B (AT-rich interactive domain-containing protein 1B) gene mutation is associated with intellectual disability and autism spectrum disorders, but the researchers have not yet found out how these mutations contribute to clinical manifestations. To determine the effect of gene mutations and its features, a team of researchers led by Dr. Hao Zhu and Cemre Celen genetically modified mice to carry a mutation in one of two copies of the ARID1B gene. This mutation replicates genetics of Coffin-Siris syndrome. It is characterized by impaired speech and social development, intellectual disability, and delayed physical growth. Understanding the molecular basis of Coffin-Siris syndrome is thought to provide a better understanding of similar disorders.
The researchers found that mice with the mutated ARID1B gene exhibited similar manifestations as of Coffin-Siris syndrome. Impaired mental development, muscle weakness, increased anxiety and fear, autism spectrum disorder (social interaction abnormalities, repetitive behaviors, and abnormal "squeaks" or vocalizations) were observed in the mice. Also, the growth hormone and insulin-like growth factor (IGF1) levels in the blood were reduced, resulting in small stature and delayed development in humans. Treating the mutated mice with growth hormones restored body size and muscle function, but behavioral changes associated with the disorder remained the same.
Dr. Zhu, an Assistant Professor at CRI, stated that "These results suggest that growth hormone treatment could be a useful therapy for ARID1B patients. This is an interesting finding because we know some pediatricians already treat Coffin-Siris patients with growth hormones, although they were unaware that this response might be common to many people with ARID1B mutations."
The study provided the researchers with an important model to carry out further studies about ARID1B's role in human brain disorders and facilitate therapeutic testing of potential treatments for autism, intellectual disability, and Coffin-Siris syndrome with its aid.