Research on Brain Disease in Pugs Could Also Help Scientists Understand A Rare Form of Multiple Sclerosis

Toy dogs may be small and cute, but that doesn’t mean they can’t suffer from some very big and ugly health problems. There are a number of serious, and often fatal, inflammatory diseases of the brain and spinal cord seen in toy breeds. Although these conditions have been recognized as a problem for several decades, their causes have largely remained unexplained.

That may be changing. In recent years, there has been a growing body of evidence suggesting that many, or all, of this group of breed-specific degenerative nervous system conditions may be auto-immune in origin. In fact, there is a growing suspicion that these diseases could be related to the human disease known as multiple sclerosis (MS).

Thanks to a grant from the AKC Canine Health Foundation, scientists are now much closer to understanding how strong that similarity actually may be. A group of researchers looking at the genetic causes of one of these inflammatory brain conditions, necrotizing meningoencephalitis (NME), have found that disease risk in Pug Dogs is closely linked to the same group of genes that has been implicated in human risk for MS.

A whole genome scan of Pug dogs with and without NME found that the single genetic association for the disease was with the dog leukocyte antigen (DLA) complex – a group of genes analogous to the human leukocyte antigen (HLA) complex. However, the 2010 study, published by Dr. Kimberly Greer and her colleagues, didn’t stop there. It also delved further to discover that the specific sequence variants that were highly correlated to a Pug’s risk of developing NME were in the same genes that have been shown to be associated with human risk of MS.

Necrotizing meningoencephalitis, also known as Pug Dog Encephalitis (PDE), is an aggressive brain disease that can lead to death within months, weeks, or even days, of onset. Although the most common forms of MS progress far more slowly than NME, relapsing and remitting for years or even decades, there are certain acute forms of MS that behave more like the Pug condition. As with NME, these severe progressive forms of MS occur more often in females than in males and have a younger age of onset than the more commonly observed types. Thus, although NME isn’t a perfect model for MS, this naturally occurring dog disease could still provide scientists with important insights about how similar inflammatory brain diseases progress in humans.

The long term implications, at least for Pugs, remain mixed. Breedings dogs to bring out desirable traits can also unknowingly amplify the presence of harmful conditions. That is certainly the case for NME in Pugs. In this study, 11 percent of dogs had two copies of the genetic sequence associated with the highest risk of NME and a full 29 percent had a single copy of the variant.

Although genetic testing could help breeders limit the number of puppies at the highest level of danger, those with two copies of the gene, it is impossible to even consider weeding the problematic mutation out of the Pug genome entirely. Pugs are already a relatively homogeneous group, with 87 percent of the breed traceable back to a single male ancestor. Trying to eliminate every copy of the high-risk variant would cause a further loss in genetic diversity, and there’s a real possibility that doing so could lead to more problems than it would solve.

This work was funded by AKC Canine Health Foundation Grant 640.

Scientific publication: