Hereditary polymyositis in the Dutch Kooiker dog

This PhD thesis investigates a long-term inherited muscle inflammation, called polymyositis, in the Dutch Kooiker dog and is based on five published studies. These studies contribute to a better understanding of these conditions in this breed. The first study, titled “An Inflammatory Myopathy in the Dutch Kooiker Dog”, describes the clinical signs, blood test results, and muscle tissue analysis. Affected dogs showed problems with walking and/or swallowing. Blood tests showed increased levels of muscle enzymes. Muscle tissue analysis revealed immune cells entering and damaging the muscle fibres. The second study, “Pathologic Changes in and Immunophenotyping of Polymyositis in the Dutch Kooiker Dog”, further examined the affected muscle tissue. Under the microscope, signs of inflammation were seen, with immune cells invading healthy muscle fibres and surrounding tissue, causing damage and muscle cell death. Most of the invading cells were types of white blood cells; the muscle cells themselves showed involvement in the immune response. These findings are typical for polymyositis. The third study, “Polymyositis in Kooiker dogs is associated with a 39 kb deletion upstream of the canine IL21/IL2 locus”, identified a genetic abnormality linked to the disease. The study found that affected dogs were missing a significant section of DNA, which caused two genes linked to immune system diseases to become more active. Based on this, dogs with two copies of the deletion have a 10–20% lifetime risk of developing this muscle inflammation, while dogs with one copy have a 0.5–2% risk. The fourth study, “Magnetic resonance imaging characteristics of hereditary polymyositis in the Dutch Kooiker dog”, evaluated MRI as a tool to diagnose the disease. Dogs with symptoms showed abnormal muscles on MRI, while healthy dogs did not. The study concludes that MRI is a useful, non-invasive test for identifying the condition and may help screen dogs with the DNA error. However, microscopic examination of the muscle tissue remains the definitive diagnostic method. The final study of this PhD thesis, "Age of onset, treatment response, and survival rates in Dutch Kooiker dogs diagnosed with hereditary polymyositis”, assessed three treatment plans: 1) immune system inhibitor alone, 2) immune inhibitor combined with supplements (vitamin B, L-carnitine, and coenzyme Q10), and 3) immune inhibitor combined with supplements and a drug that modifies immune system activity, called oclacitinib. The combination including oclacitinib was linked to the longest survival and appeared to be the most effective in this study. Together, these studies have advanced our understanding of hereditary muscle inflammation in the Dutch Kooiker dog. Future efforts to improve the breed’s health should focus on breeding strategies and broader study of the disease’s causes. One key goal is to look for another genetic change that may play a role to the condition. Further research into the immune mechanisms behind muscle inflammation could also lead to new treatments.