Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model

Abstract

Cardiac disease is a leading cause of death for both humans and dogs. Genetic cardiomyopathies, including dilated cardiomyopathy (DCM), account for a proportion of these cases in both species. Patients may suffer from ventricular enlargement and systolic dysfunction resulting in congestive heart failure and ventricular arrhythmias with high risk for sudden cardiac death. Although canine DCM has similar disease progression and subtypes as in humans, only a few candidate genes have been found to be associated with DCM while the genetic background of human DCM has been more thoroughly studied. Additionally, experimental disease models using induced pluripotent stem cells have been widely adopted in the study of human genetic cardiomyopathy but have not yet been fully adapted for the in-depth study of canine genetic cardiomyopathies. The clinical presentation of DCM is extremely heterogeneous for both species with differences occurring based on sex predisposition, age of onset, and the rate of disease progression. Both genetic predisposition and environmental factors play a role in disease development which are identical in dogs and humans in contrast to other experimental animals. Interestingly, different dog breeds have been shown to develop distinct DCM phenotypes, and this presents a unique opportunity for modeling as there are multiple breed-specific models for DCM with less genetic variance than human DCM. A better understanding of DCM in dogs has the potential for improved selection for breeding and could lead to better overall care and treatment for human and canine DCM patients. At the same time, progress in research made for human DCM can have a positive impact on the care given to dogs affected by DCM. Therefore, this review will analyze the feasibility of canines as a naturally occurring bidirectional disease model for DCM in both species. The histopathology of the myocardium in canine DCM will be evaluated in three different breeds compared to control tissue, and the known genetics that contributes to both canine and human DCM will be summarized. Lastly, the prospect of canine iPSCs as a novel method to uncover the contributions of genetic variants to the pathogenesis of canine DCM will be introduced along with the applications for disease modeling and treatment.

An ABCC9 Missense Variant Is Associated with Sudden Cardiac Death and Dilated Cardiomyopathy in Juvenile Dogs

“…The present discovery adds to a growing list of shared susceptibility genes for sudden cardiac death and DCM between dogs and humans [59]. For example, variants in KCNQ1 (potassium voltage-gated channel subfamily Q member 1) are one of the most common causes of long QT syndrome in humans, and a KCNQ1 variant is associated with this syndrome in dogs [13,60].…”

Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human

“…The complex genetic cause of disease against a more homogeneous background due to inbreeding enables the discovery of minor genes involved in DCM. Comprehensive One Health approaches in the future will lead to a better understanding of DCM and have the potential to lead to better overall care and treatment [ 13 ].…”

Діагностика Кардіоміопатії У Свійських Собак

“…Ця патологія провокує порушення функції серця та спричиняє серцеву недостатність [3,2]. Згідно з даними літературних джерел, кардіоміопатія може виникати в різних формах і класифікують її залежно від характеристик і типу ураження міокарду [4,3].…”

“…Shen L. та ін. (2022) і Gaar-Humphreys K. зі співавторами (2022) зазначали, що такі породи свійських собак як боксер, доберман, лабрадор ретривер та німецька вівчарка частіше хворіють на кардіоміопатію внаслідок породної схильності [2,4], саме тому ми обрали ці породи для діагностики.…”