Mouse illutration

Model Organism: House Mouse (Mus musculus)

Phylum: Chordata

The top mammal model, mice develop diseases that affect humans, like cancer and diabetes. As mice age 30x faster than humans, they teach us about aging. The mouse genome contains 3.1 billion DNA base pairs.

House mouse: providing insights into the genetics of autism

As the top mammal model organism, mice develop diseases that affect humans, like cancer and diabetes. Because mice and humans share on average 85 percent of similarly coded genes, mice can be used as a model to study how genetic mutations impact brain development. Changes in mouse DNA mimic changes in human DNA and vice-versa. In addition, mice exhibit behaviors that can be used as models for exploring human behavior.

Taking advantage of the house mouse and advances in genetic technologies, researchers led by Alex Nord, assistant professor of neurobiology, physiology and behavior are gaining a better understanding of the role played by a specific gene involved in autism spectrum disorders (ASD).

While there is no known specific genetic cause for most cases of autism, many different genes have been linked to the disorder. In rare, specific cases of people with ASD, one copy of a gene called CHD8 is mutated and loses function. The CHD8 gene encodes a protein responsible for packaging DNA in cells throughout the body.

Nords laboratory at UC Davis and his collaborators are working to characterize changes in brain development and behavior of mice carrying a mutated copy of CHD8.

Behavioral tests with mice give us information about sociability, anxiety and cognition,” said Nord. "From there, we can examine changes at the anatomical and cellular level to find links across dimensions. This is critical to understanding the biology of disorders like autism.”

By inducing mutation of the CHD8 gene in mice and studying their brain development, Nord and his team have established that the mice experience cognitive impairment and have increased brain volume. Both of these conditions are present in individuals with a mutated CHD8 gene.

Mutations in CHD8 lead to excessive production of dividing cells in the brain, as well as megalencephaly, an enlarged brain condition common in individuals with ASD. These findings suggest the developmental causes of increased brain size.

More surprisingly, Nord also discovered that pathological changes in gene expression in the brains of mice with a mutated CHD8 continued through the mice’s lifetime. Genes involved in critical biological processes like synapse function were impacted by the CHD8 mutation too. This suggests that CHD8 plays a role in brain function throughout life and may affect more than early brain development in autistic individuals.

While Nords research centers on severe ASD conditions, the lessons learned may eventually help explain many cases along the autism spectrum.

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