Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model
Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands
Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands
Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands
Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands
Department of Pathology, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands
Department of Genetics, University Medical Center Utrecht, Utrecht University, 3508 AB Utrecht, The Netherlands
Institute of Cardiovascular Science, Faculty Population Health Sciences, University College London, London WC1E 6BT, UK
Health Data Research UK and Institute of Health Informatics, University College London, London WC1E 6BT, UK
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Cedric Gondro
Received: 7 April 2022
Revised: 16 June 2022
Accepted: 25 June 2022
Published: 29 June 2022
Heart disease is a leading cause of death for both humans and dogs. Inherited heart diseases, including dilated cardiomyopathy (DCM), account for a proportion of these cases. Human and canine patients with DCM suffer from an enlarged heart that can no longer pump efficiently, resulting in heart failure. This causes symptoms or clinical signs like difficulty breathing, irregular heartbeat, and eventually death. The symptoms or clinical signs of this disease vary in age of onset at the beginning of symptoms, sex predisposition, and overall disease progression. Despite the many similarities in DCM in both species, only a few candidate genes so far have been linked to this disease in dogs versus tens of genes identified in human DCM. Additionally, the use of induced pluripotent stem cells, or engineered stem cells, has been widely used in the study of human genetic heart disease but has not yet been fully adapted to study heart disease in dogs. This review describes the current knowledge on the genetics and subtypes of naturally occurring DCM in dogs, and how advances in research might benefit the dog but also the human patient. Additionally, a novel method using canine engineered stem cells to uncover unknown contributions of mistakes in DNA to the progression of DCM will be introduced along with its applications for human DCM disease modeling and treatment.