Searching for the Genetic Basis of Addison’s Disease in the Bearded Collie

Addison’s Disease (AD, or hypoadrenocorticism) is an autoimmune disease caused by destruction of the outer layer of the adrenal glands. This section of the adrenal glands is responsible for making steroid hormones which help the body adapt and respond to stress. When immune cells infiltrate the adrenal glands and make antibodies against steroid-producing cells, a life-threatening decrease in steroid hormone production results. Symptoms can be vague and intermittent at first – such as lethargy and mild vomiting or diarrhea. Eventually, when steroid levels reach a critically low level, the dog will experience an “Addisonian crisis” with cardiovascular shock, low blood sugar, and abnormal heart rhythms. While AD can be difficult to diagnose, treatment is relatively simple and consists of providing the hormones no longer made by the body.

AD occurs in all dog breeds and mixed breeds. However, it is more prevalent in certain breeds (Bearded Collies, Portuguese Water Dogs, Standard Poodles, West Highland White Terriers, Leonbergers, Wheaten Terriers, and Nova Scotia Duck Tolling Retrievers), suggesting a genetic component to its development. The disease is also seen in humans and previous studies of canine AD have implicated many of the same genes that are involved in human AD. While humans and dogs may share some of the genetic causes of AD, there are breed-specific genetic changes in dogs that need further study. To address this need, the AKC Canine Health Foundation (CHF) and its donors have invested in numerous studies on the genetic basis of AD in at risk breeds, including the Portuguese Water Dog, Nova Scotia Duck Tolling Retriever, Bearded Collie, and more. Several of these studies have been conducted by CHF Clinician-Scientist Fellows, demonstrating the success of CHF’s programs to encourage new canine health researchers. (Learn more about this program at akcchf.org/clinsci.)

CHF-funded investigators at the University of California, Davis analyzed DNA from 59 Bearded Collies with AD and 84 control dogs (Bearded Collies that were at least 10 years old and had never experienced an autoimmune disease). Results were recently published in BMC Genomics¹ and describe one region found on canine chromosome 18 with mutations that were significantly associated with the diagnosis of AD. They also identified three additional gene regions that had a lower level of association with the diagnosis of AD. As the number of abnormal genes increased, so did an individual dog’s risk of developing AD. That is, dogs with the mutation on chromosome 18 and one or more of the other abnormal gene sets had a higher risk of clinical AD compared to dogs with none of them. This supports our understanding that AD is a complex, polygenic disease requiring the accumulation of multiple genetic changes and environmental influences to produce clinical disease.

Additional study is needed to confirm these findings and detail the specific mutations that cause AD in Bearded Collies and other dog breeds. This knowledge will allow more accurate and early diagnosis of AD, plus allow breeders to manage the risk of AD in their breeding plans, producing fewer affected dogs. CHF and its donors remain committed to discovering the genetic causes of canine diseases such as AD and more so that all dogs may live longer, healthier lives. Learn more about these studies at akcchf.org/research.

Related CHF grants:
02187-MOU: Investigating Symmetrical Lupoid Onychodystrophy in Bearded Collies
01236-A: Hypothyroidism and Autoimmune Susceptibility Genes in the Bearded Collie
02428: Identifying the Disease-Defining Autoantibodies in Canine Addison's Disease
02488: Addison's Disease and Symmetrical Lupoid Onychodystrophy in Bearded Collies Provide Common Ground for Identifying Susceptibility Loci Underlying Canine Autoimmune Disorders
02805-E – 2020 Clinician-Scientist Fellowship; Liza Crissiuma Gershony, DVM, PhD

References:
1. Gershony, L. C., Belanger, J. M., Hytönen, M. K., Lohi, H., Famula, T. R., & Oberbauer, A. M. (2020). Genetic characterization of Addison’s disease in Bearded Collies. BMC Genomics, 21(1), 833.