Researchers at the UC San Diego School of Medicine have developed a mouse model that connects the genetic defects of Jacobsen syndrome to effects on brain function consistent with autism disorders.
About half of children with Jacobsen syndrome experience social and behavioral issues consistent with autism disorders.
"While this study focused on mice with a specific type of genetic mutation that led to autism-like symptoms, these findings could lead to a better understanding of the molecular mechanisms underlying other autism spectrum disorders, and provide a guide for the development of new potential therapies," said study co-author Paul Grossfeld, MD, clinical professor of pediatrics at UC San Diego School of Medicine and pediatric cardiologist at Rady Children's Hospital-San Diego.
The study also found the anti-anxiety drug clonazepam reduces autistic features in the Jacobsen syndrome mice.
Jacobsen syndrome is a rare genetic disorder in which a child is born missing a portion of one copy of chromosome 11.
The gene loss can lead to multiple clinical challenges, such as congenital heart disease, intellectual disability, developmental and behavioral problems, slow growth and failure to thrive.
Previous research by Grossfield and others suggested that PX-RICS, the dominant isoform expressed in nervous system development, might be the missing chromosome 11 gene in children with Jacobsen syndrome.
Researchers at the University of Tokyo found PX-RICS to be the most likely gene responsible for autism-like symptoms in Jacobsen syndrome.
They found mice without PX-RICS were less social and more apathetic to other mice. They also spent twice as much time on repetitive behaviors than mice with the gene and were less able to adapt to new situations. They found mice lacking PX-RICS were also deficient in GABAAR, a protein crucial for normal neuron function.
PX-RICS-deficient mice treated with clonazepam, which works by boosting GABAAR, behaved almost normally in social tests, experienced improvements in learning performance and were better able to deviate from established habits.
"We now hope in the future to carry out a small pilot clinical trial on people with Jacobsen syndrome and autism to determine if clonazepam might help improve their autistic features," Grossfeld said.
Study co-authors include Tsutomu Nakamura, Fumiko Arima-Yoshida, Fumika Sakaue, Yukiko Nasu-Nishimura, Yasuko Takeda, Ken Matsuura, Toshiya Manabe, Tetsu Akiyama, University of Tokyo; Natacha Ackshoomoff, UC San Diego; and Sarah Mattson, San Diego State University.