Gene for Fatal Brain Disorder Discovered in Dogs

LiveScience Staff

Date: 24 August 2010 Time: 01:27 AM ET

Researchers have isolated the gene responsible for a fatal brain disease in American Staffordshire terriers, according to a new report. Not only will the finding help diagnose the disorder in dogs, it may be a first step to finding a similar gene in humans.

The disease, known as neuronal ceroid lipofuscinosis, or NCL for short, affects one out of every 400 American Staffordshire terriers. It usually strikes in adulthood, and is marked by a buildup of fatty substances called lipofuscin in the brain. This buildup kills brain cells in the cerebellum, an area important for motor control. Unable to walk or control their muscles, dogs eventually die or have to be euthanized.

In humans, NCLs have similar neurodegenerative effects, ranging from blindness to loss of motor function to death. In children, the disease is known as Batten or Jansky-Bielschowsky disease, while a similar disorder in adults is called Kufs'.

Researchers have long known that NCLs are caused by a recessive gene mutation. Animals (and people) with one copy of the gene are carriers. They don't get the disease, but can pass it on to their offspring. Two copies of the mutation cause full-blown disease.

In dogs, "the disease became so prevalent because it was a recessive disease with a late onset," said Natasha Olby, a neurologist at North Carolina State University who was part of the international team of researchers who isolated the gene. "Carriers of a single copy of the mutated gene never develop symptoms, and dogs with two copies of the gene might not show symptoms until five or six years of age, so the mutation was able to take hold in the breeding population."

Through a genetic analysis of the American Staffordshire genome, the researchers were able to identify the location of the mutation on a gene called Arylsulfatase G. The mutation leads to a 75-percent drop in the activity of an enzyme called sulfatase, suggesting that a lack of this enzyme plays a role in NCLs.

The next step is to test the genomes of adults with Kufs' disease to find out whether the same gene is responsible for that brain disorder, the researchers said.

"The canine disease is a good model of the adult human form of the disease," Olby said. "We hope that this discovery will provide insight into the development of the disease."

The findings were published Aug. 17 in the Proceedings of the National Academy of Sciences.