Gene mutation linked to abnormal brain development in dogs and humans: Study

(Wang et al./Cell Reports 2016)

Scientists have identified a mutation that causes uncoordinated muscle movements in humans and dogs. The finding could prove useful for pharma companies developing treatments for neurodegenerative diseases.

Researchers found that a mutation in the CAPN1 gene disrupts the function of an enzyme called calpain-1 and causes abnormal brain development in humans, mice and Parson Russell Terrier dogs. The team published their findings in a recent issue of Cell Reports.

Scientists have examined mutations linked to calpain, which comes in two major forms: calpain-1 and calpain-2. But it was difficult to distinguish between the two forms because many drug studies used molecules that inhibit both types of the enzyme, Michael Baudry, a neurobiologist at Western University of Health Sciences, said in a statement.

So Baudy and his team decided to study a line of mice genetically engineered to only have calpain-1 to look at the differences between the two forms. Another team at University College London, led by neurologist Henry Houlden, also joined the study.

Researchers found that mice with no calpain-1 due to the CAPN1 mutation had mild cerebellar ataxia. During the first week after birth, mice without calpain-1 also had a higher rate of neuronal death in the cerebellum compared to normal mice and stunted synapse development.

The findings could shed light on neurodegenerative drug development. Calpain inhibitors may not work correctly because they don’t distinguish between calpain-1 and calpain-2, and calpain-2 inhibitor is needed to address neurodegeneration, Baudry said.

The recent study shows that there “are a number of genes linked to motor function that can be involved in ataxia when mutated," Baudry said. "Not only have we identified another, but we've also refined our understanding of the calpain enzymes, which is important because several companies have been talking about using calpain inhibitors to treat neurodegenerative diseases."

- here’s the study abstract
- read the statement

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