{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:58:05Z","timestamp":1790330285815,"version":"4.1.0"},"reference-count":109,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Cardiovascular Alliance (DCVA) study Double-Dose","award":["2020B005"],"award-info":[{"award-number":["2020B005"]}]},{"name":"Dutch Cardiovascular Alliance (DCVA) study Double-Dose","award":["09120012010018"],"award-info":[{"award-number":["09120012010018"]}]},{"name":"Dutch Cardiovascular Alliance (DCVA) study Double-Dose","award":["18CVD01"],"award-info":[{"award-number":["18CVD01"]}]},{"name":"Dutch Cardiovascular Alliance (DCVA) study Double-Dose","award":["2019T109"],"award-info":[{"award-number":["2019T109"]}]},{"name":"Dutch Cardiovascular Alliance (DCVA) study Double-Dose","award":["LSHM20093"],"award-info":[{"award-number":["LSHM20093"]}]},{"name":"ZonMW Open Competition study CONTRACT","award":["2020B005"],"award-info":[{"award-number":["2020B005"]}]},{"name":"ZonMW Open Competition study CONTRACT","award":["09120012010018"],"award-info":[{"award-number":["09120012010018"]}]},{"name":"ZonMW Open Competition study CONTRACT","award":["18CVD01"],"award-info":[{"award-number":["18CVD01"]}]},{"name":"ZonMW Open Competition study CONTRACT","award":["2019T109"],"award-info":[{"award-number":["2019T109"]}]},{"name":"ZonMW Open Competition study CONTRACT","award":["LSHM20093"],"award-info":[{"award-number":["LSHM20093"]}]},{"name":"Leducq Foundation study CURE-PLaN","award":["2020B005"],"award-info":[{"award-number":["2020B005"]}]},{"name":"Leducq Foundation study CURE-PLaN","award":["09120012010018"],"award-info":[{"award-number":["09120012010018"]}]},{"name":"Leducq Foundation study CURE-PLaN","award":["18CVD01"],"award-info":[{"award-number":["18CVD01"]}]},{"name":"Leducq Foundation study CURE-PLaN","award":["2019T109"],"award-info":[{"award-number":["2019T109"]}]},{"name":"Leducq Foundation study CURE-PLaN","award":["LSHM20093"],"award-info":[{"award-number":["LSHM20093"]}]},{"name":"ERA-CVD study SCALE","award":["2020B005"],"award-info":[{"award-number":["2020B005"]}]},{"name":"ERA-CVD study SCALE","award":["09120012010018"],"award-info":[{"award-number":["09120012010018"]}]},{"name":"ERA-CVD study SCALE","award":["18CVD01"],"award-info":[{"award-number":["18CVD01"]}]},{"name":"ERA-CVD study SCALE","award":["2019T109"],"award-info":[{"award-number":["2019T109"]}]},{"name":"ERA-CVD study SCALE","award":["LSHM20093"],"award-info":[{"award-number":["LSHM20093"]}]},{"name":"LSH-TKI study Dog2Human","award":["2020B005"],"award-info":[{"award-number":["2020B005"]}]},{"name":"LSH-TKI study Dog2Human","award":["09120012010018"],"award-info":[{"award-number":["09120012010018"]}]},{"name":"LSH-TKI study Dog2Human","award":["18CVD01"],"award-info":[{"award-number":["18CVD01"]}]},{"name":"LSH-TKI study Dog2Human","award":["2019T109"],"award-info":[{"award-number":["2019T109"]}]},{"name":"LSH-TKI study Dog2Human","award":["LSHM20093"],"award-info":[{"award-number":["LSHM20093"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ani12131679","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T20:47:56Z","timestamp":1656535676000},"page":"1679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2851-4380","authenticated-orcid":false,"given":"Karen R.","family":"Gaar-Humphreys","sequence":"first","affiliation":[{"name":"Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talitha C. F.","family":"Spanjersberg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"},{"name":"Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Santarelli","sequence":"additional","affiliation":[{"name":"Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1583-9648","authenticated-orcid":false,"given":"Guy C. M.","family":"Grinwis","sequence":"additional","affiliation":[{"name":"Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0273-6586","authenticated-orcid":false,"given":"Viktor","family":"Szatm\u00e1ri","sequence":"additional","affiliation":[{"name":"Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9512-4708","authenticated-orcid":false,"given":"Bernard A. J.","family":"Roelen","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"},{"name":"Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9371-8788","authenticated-orcid":false,"given":"Aryan","family":"Vink","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3854-6749","authenticated-orcid":false,"given":"J. Peter","family":"van Tintelen","sequence":"additional","affiliation":[{"name":"Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands"},{"name":"Department of Genetics, University Medical Center Utrecht, Utrecht University, 3508 AB Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-8669","authenticated-orcid":false,"given":"Folkert W.","family":"Asselbergs","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands"},{"name":"Institute of Cardiovascular Science, Faculty Population Health Sciences, University College London, London WC1E 6BT, UK"},{"name":"Health Data Research UK and Institute of Health Informatics, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hille","family":"Fieten","sequence":"additional","affiliation":[{"name":"Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Harakalova","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5460-6540","authenticated-orcid":false,"given":"Frank G.","family":"van Steenbeek","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"},{"name":"Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"ref_1","first-page":"204823","article-title":"Genetics of Human and Canine Dilated Cardiomyopathy","volume":"2015","author":"Simpson","year":"2015","journal-title":"Int. J. Genom."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/CIRCRESAHA.117.308903","article-title":"Reducing the Global Burden of Cardiovascular Disease, Part 1: The Epidemiology and Risk Factors","volume":"121","author":"Joseph","year":"2017","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1111\/j.1939-1676.2006.tb01803.x","article-title":"Heart Disease as a Cause of Death in Insured Swedish Dogs Younger Than 10 Years of Age","volume":"20","author":"Egenvall","year":"2006","journal-title":"J. Veter. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"d6966","DOI":"10.1136\/bmj.d6966","article-title":"Inherited cardiomyopathies","volume":"343","author":"Raju","year":"2011","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nrcardio.2013.105","article-title":"Dilated cardiomyopathy: The complexity of a diverse genetic architecture","volume":"10","author":"Hershberger","year":"2013","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mausberg, T.-B., Wess, G., Simak, J., Keller, L., Dr\u00f6gem\u00fcller, M., Dr\u00f6gem\u00fcller, C., Webster, M., Stephenson, H., Dukes-McEwan, J., and Leeb, T. (2011). A Locus on Chromosome 5 Is Associated with Dilated Cardiomyopathy in Doberman Pinschers. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020042"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11259-007-0005-8","article-title":"Animal Models of Dilated Cardiomyopathy for Translational Research","volume":"31","author":"Recchia","year":"2007","journal-title":"Veter- Res. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rodgers, J.L., Jones, J., Bolleddu, S.I., Vanthenapalli, S., Rodgers, L.E., Shah, K., Karia, K., and Panguluri, S.K. (2019). Cardiovascular Risks Associated with Gender and Aging. J. Cardiovasc. Dev. Dis., 6.","DOI":"10.3390\/jcdd6020019"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1292\/jvms.15-0171","article-title":"Association between breed, gender and age in relation to cardiovascular disorders in insured dogs in Japan","volume":"78","author":"Inoue","year":"2016","journal-title":"J. Veter- Med Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"672039","DOI":"10.3389\/fcell.2021.672039","article-title":"Uncovering Inherited Cardiomyopathy With Human Induced Pluripotent Stem Cells","volume":"9","author":"Jiang","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41551-019-0348-9","article-title":"Combinatorial interactions of genetic variants in human cardiomyopathy","volume":"3","author":"Deacon","year":"2019","journal-title":"Nat. Biomed. Eng."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41572-019-0084-1","article-title":"Dilated cardiomyopathy","volume":"5","author":"Schultheiss","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1177\/0300985820906895","article-title":"Canine Dilated Cardiomyopathy: Diffuse Remodeling, Focal Lesions, and the Involvement of Macrophages and New Vessel Formation","volume":"57","author":"Gasparini","year":"2020","journal-title":"Veter. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s00059-020-04903-5","article-title":"Dilated cardiomyopathies and non-compaction cardiomyopathy","volume":"45","author":"Veltmann","year":"2020","journal-title":"Herz"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"34","author":"Caforio","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1161\/CIRCRESAHA.117.311812","article-title":"Cardiomyopathies","volume":"121","author":"Braunwald","year":"2017","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/978-1-0716-0904-0_14","article-title":"Precision Medicine and Dilated Cardiomyopathy","volume":"2204","author":"Li","year":"2020","journal-title":"Precis. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1136\/inpract.22.10.620","article-title":"Canine dilated cardiomyopathy 2. Pathophysiology and treatment","volume":"22","author":"McEwan","year":"2000","journal-title":"Practice"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1053\/tvjl.2001.0616","article-title":"Canine Idiopathic Dilated Cardiomyopathy. Part II: Pathophysiology and therapy","volume":"162","author":"Borgarelli","year":"2001","journal-title":"Vet. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1097\/GIM.0b013e3181f2481f","article-title":"Clinical and genetic issues in dilated cardiomyopathy: A review for genetics professionals","volume":"12","author":"Hershberger","year":"2010","journal-title":"Genet. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/oxfordjournals.eurheartj.a059861","article-title":"Non-invasive assessmenty of systolic left ventricular function in systemic sclerosis","volume":"12","author":"Kazzam","year":"1991","journal-title":"Eur. Heart J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0167-5273(92)90082-E","article-title":"Symptomatic cardiac involvement in juvenile rheumatoid arthritis","volume":"34","author":"Goldenberg","year":"1992","journal-title":"Int. J. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"381","DOI":"10.2143\/AC.56.6.2005702","article-title":"Evaluation of myocarial involvement in systemic lupus erythematosus by signal-averaged electrocardiography and echocardiography","volume":"56","author":"Paradiso","year":"2001","journal-title":"Acta Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"skaa155","DOI":"10.1093\/jas\/skaa155","article-title":"Review of canine dilated cardiomyopathy in the wake of diet-associated concerns","volume":"98","author":"McCauley","year":"2020","journal-title":"J. Anim. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15563650.2018.1497172","article-title":"Mechanisms of toxic cardiomyopathy","volume":"57","author":"Hantson","year":"2018","journal-title":"Clin. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15881","DOI":"10.1038\/s41598-021-94464-2","article-title":"Investigation of diets associated with dilated cardiomyopathy in dogs using foodomics analysis","volume":"11","author":"Smith","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_27","first-page":"98","article-title":"Myocardial diseases of animals","volume":"124","author":"Ferrans","year":"1986","journal-title":"Am. J. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1177\/0148607189013006663","article-title":"Reversible Cardiomyopathy Due to Selenium Deficiency","volume":"13","author":"Reeves","year":"1989","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.tcm.2018.07.012","article-title":"Peripartum cardiomyopathy-diagnosis, management, and long term implications","volume":"29","author":"Stergiopoulos","year":"2018","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1136\/heart.84.1.106","article-title":"CARDIOMYOPATHY: Diagnosis and management of dilated cardiomyopathy","volume":"84","author":"Elliott","year":"2000","journal-title":"Heart"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1111\/j.1939-1676.2012.00987.x","article-title":"Screening for Dilated Cardiomyopathy in Great Danes in the United Kingdom","volume":"26","author":"Stephenson","year":"2012","journal-title":"J. Veter. Intern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1760-2734(06)70047-9","article-title":"Proposed Guidelines for the Diagnosis of Canine Idiopathic Dilated Cardiomyopathy","volume":"5","author":"Borgarelli","year":"2003","journal-title":"J. Veter. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/j.1748-5827.1999.tb03102.x","article-title":"Observations on the development of congestive heart failure in Irish wolfhounds with dilated cardiomyopathy","volume":"40","author":"Brownlie","year":"1999","journal-title":"J. Small Anim. Pr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1354\/vp.42-1-1","article-title":"Histologic Characterization of Canine Dilated Cardiomyopathy","volume":"42","author":"Tidholm","year":"2005","journal-title":"Veter. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"729","DOI":"10.2460\/javma.2001.218.729","article-title":"Clinical features of dilated cardiomyopathy in Great Danes and results of a pedigree analysis: 17 cases (1990-2000)","volume":"218","author":"Meurs","year":"2001","journal-title":"J. Am. Veter. Med Assoc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1939-1676.1997.tb00474.x","article-title":"Signalment, Survival, and Prognostic Factors in Doberman Pinschers with End-Stage Cardiomyopathy","volume":"11","author":"Calvert","year":"1997","journal-title":"J. Veter. Intern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.cmet.2013.06.016","article-title":"Fibrosis and Adipose Tissue Dysfunction","volume":"18","author":"Sun","year":"2013","journal-title":"Cell Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1177\/0300985810364511","article-title":"Histologic Characterization of Dilated Cardiomyopathy in Estrela Mountain Dogs","volume":"47","author":"Lobo","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1365-2559.1984.tb02351.x","article-title":"The cardiomyopathies: A review of terminology, pathology and pathogenesis","volume":"8","author":"Davies","year":"1984","journal-title":"Histopathology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.hrthm.2017.03.034","article-title":"Distinct fibrosis pattern in desmosomal and phospholamban mutation carriers in hereditary cardiomyopathies","volume":"14","author":"Sepehrkhouy","year":"2017","journal-title":"Heart Rhythm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/jsap.12841","article-title":"An update on canine cardiomyopathies\u2014Is it all in the genes?","volume":"59","author":"Dutton","year":"2018","journal-title":"J. Small Anim. Pr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jvc.2021.05.003","article-title":"A review of the underlying genetics and emerging therapies for canine cardiomyopathies","volume":"40","author":"Shen","year":"2021","journal-title":"J. Veter. Cardiol."},{"key":"ref_43","first-page":"1319","article-title":"A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher","volume":"131","author":"Meurs","year":"2012","journal-title":"Qual. Life Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3930","DOI":"10.1038\/s41598-020-60879-6","article-title":"Functional Consequences of PDK4 Deficiency in Doberman Pinscher Fibroblasts","volume":"10","author":"Bolfer","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1089\/biores.2017.0023","article-title":"PDK4 Deficiency Induces Intrinsic Apoptosis in Response to Starvation in Fibroblasts from Doberman Pinschers with Dilated Cardiomyopathy","volume":"6","author":"Taggart","year":"2017","journal-title":"BioResearch Open Access"},{"key":"ref_46","first-page":"515","article-title":"A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death","volume":"138","author":"Meurs","year":"2019","journal-title":"Qual. Life Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/j.1939-1676.2010.0479.x","article-title":"Prevalence of Dilated Cardiomyopathy in Doberman Pinschers in Various Age Groups","volume":"24","author":"Wess","year":"2010","journal-title":"J. Veter. Intern. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.2460\/javma.2020.257.10.1041","article-title":"Assessment of PDK4 and TTN gene variants in 48 Doberman Pinschers with dilated cardiomyopathy","volume":"257","author":"Meurs","year":"2020","journal-title":"J. Am. Veter. Med Assoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"125","DOI":"10.5326\/15473317-36-2-125","article-title":"The prevalence of cardiomyopathy in the Irish wolfhound: A clinical study of 500 dogs","volume":"36","author":"Vollmar","year":"2000","journal-title":"J. Am. Anim. Hosp. Assoc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/sj.hdy.6801024","article-title":"Complex segregation analysis of dilated cardiomyopathy (DCM) in Irish wolfhounds","volume":"99","author":"Distl","year":"2007","journal-title":"Heredity"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/jvim.13914","article-title":"Long-term Outcome of Irish Wolfhound Dogs with Preclinical Cardiomyopathy, Atrial Fibrillation, or Both Treated with Pimobendan, Benazepril Hydrochloride, or Methyldigoxin Monotherapy","volume":"30","author":"Vollmar","year":"2016","journal-title":"J. Veter. Intern. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6374082","DOI":"10.1155\/2016\/6374082","article-title":"Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy","volume":"2016","author":"Simpson","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Philipp, U., Vollmar, A., H\u00e4ggstr\u00f6m, J., Thomas, A., and Distl, O. (2012). Multiple Loci Are Associated with Dilated Cardiomyopathy in Irish Wolfhounds. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036691"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.gene.2019.02.022","article-title":"The R9H phospholamban mutation is associated with highly penetrant dilated cardiomyopathy and sudden death in a spontaneous canine model","volume":"697","author":"Yost","year":"2019","journal-title":"Gene"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1139\/bcb-2014-0080","article-title":"Deception in simplicity: Hereditary phospholamban mutations in dilated cardiomyopathy","volume":"93","author":"Young","year":"2015","journal-title":"Biochem. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ygeno.2008.03.007","article-title":"A novel locus for dilated cardiomyopathy maps to canine chromosome 8","volume":"91","author":"Werner","year":"2008","journal-title":"Genomics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e579","DOI":"10.1161\/CIR.0000000000000455","article-title":"Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association","volume":"134","author":"Bozkurt","year":"2016","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s11886-018-1061-0","article-title":"Genetics of Dilated Cardiomyopathy","volume":"20","author":"Fu","year":"2018","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.hjc.2018.05.008","article-title":"Current perspectives on the diagnosis and management of dilated cardiomyopathy Beyond heart failure: A Cardiomyopathy Clinic Doctor\u2019s point of view","volume":"59","author":"Bakalakos","year":"2018","journal-title":"Hell. J. Cardiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0735-1097(99)00172-2","article-title":"Familial dilated cardiomyopathy: Evidence for genetic and phenotypic heterogeneity","volume":"34","author":"Mestroni","year":"1999","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s11886-018-1030-7","article-title":"Genetics of Dilated Cardiomyopathy: Clinical Implications","volume":"20","author":"Paldino","year":"2018","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1161\/CIRCULATIONAHA.120.053033","article-title":"Evidence-Based Assessment of Genes in Dilated Cardiomyopathy","volume":"144","author":"Jordan","year":"2021","journal-title":"Circulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1752-8062.2008.00017.x","article-title":"Coding Sequence Mutations Identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 Patients with Familial or Idiopathic Dilated Cardiomyopathy","volume":"1","author":"Hershberger","year":"2008","journal-title":"Clin. Transl. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jvc.2021.05.002","article-title":"Prevalence, geographic distribution, and impact on lifespan of a dilated cardiomyopathy-associated RNA-binding motif protein 20 variant in genotyped dogs","volume":"40","author":"Leach","year":"2021","journal-title":"J. Veter. Cardiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/BF03086292","article-title":"Recurrent and founder mutations in inherited cardiac diseases in the Netherlands","volume":"17","author":"Wilde","year":"2009","journal-title":"Neth. Hear. J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1093\/eurjhf\/hfs119","article-title":"Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: Evidence supporting the concept of arrhythmogenic cardiomyopathy","volume":"14","author":"Asimaki","year":"2012","journal-title":"Eur. J. Hear. Fail."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Simpson, S., Rutland, P., and Rutland, C.S. (2017). Genomic Insights into Cardiomyopathies: A Comparative Cross-Species Review. Veter-Sci., 4.","DOI":"10.3390\/vetsci4010019"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S1760-2734(06)70041-8","article-title":"Dilated Cardiomyopathy in Juvenile Doberman Pinschers","volume":"5","author":"Vollmar","year":"2003","journal-title":"J. Veter. Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s10592-019-01240-x","article-title":"Body size, inbreeding, and lifespan in domestic dogs","volume":"21","author":"Yordy","year":"2019","journal-title":"Conserv. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ijcard.2018.10.091","article-title":"Sex-related differences in cardiomyopathies","volume":"286","author":"Pelliccia","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1002\/ejhf.1216","article-title":"Sex- and age-based differences in the natural history and outcome of dilated cardiomyopathy: Sex- and age-based differences in DCM","volume":"20","author":"Halliday","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1056\/NEJMoa1110186","article-title":"Truncations of Titin Causing Dilated Cardiomyopathy","volume":"366","author":"Herman","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s11886-020-01377-z","article-title":"Sex-Related Differences in Dilated Cardiomyopathy with a Focus on Cardiac Dysfunction in Oncology","volume":"22","author":"Camilli","year":"2020","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1093\/eurjhf\/hfs191","article-title":"Gender-specific differences in major cardiac events and mortality in lamin A\/C mutation carriers","volume":"15","author":"Nannenberg","year":"2013","journal-title":"Eur. J. Hear. Fail."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00424-018-2214-0","article-title":"Cardiomyopathy phenotypes in human-induced pluripotent stem cell-derived cardiomyocytes\u2014A systematic review","volume":"471","author":"Eschenhagen","year":"2018","journal-title":"Pfl\u00fcg Arch. Eur. J. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"281","DOI":"10.4252\/wjsc.v13.i4.281","article-title":"Patient-specific induced pluripotent stem cells as \u201cdisease-in-a-dish\u201d models for inherited cardiomyopathies and channelopathies\u201415 years of research","volume":"13","author":"Micheu","year":"2021","journal-title":"World J. Stem Cells"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2008517","DOI":"10.1002\/adma.202008517","article-title":"A Roadmap to Cardiac Tissue-Engineered Construct Preservation: Insights from Cells, Tissues, and Organs","volume":"33","author":"Janssen","year":"2021","journal-title":"Adv. Mater."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"955","DOI":"10.3389\/fbioe.2020.00955","article-title":"Cells, Materials, and Fabrication Processes for Cardiac Tissue Engineering","volume":"8","author":"Montero","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e2120887119","DOI":"10.1073\/pnas.2120887119","article-title":"DNA methylation clocks for dogs and humans","volume":"119","author":"Horvath","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-1-4939-2848-4_7","article-title":"Generation of Induced Pluripotent Stem Cells (iPSCs) from Adult Canine Fibroblasts","volume":"Volume 1330","author":"Verma","year":"2015","journal-title":"Cell Reprogramming"},{"key":"ref_82","first-page":"41","article-title":"Canine Pluripotent Stem Cells: Are They Ready for Clinical Applications?","volume":"2","author":"Betts","year":"2015","journal-title":"Front. Veter. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/rda.12562","article-title":"Derivation of Canine Induced Pluripotent Stem Cells","volume":"50","author":"Baird","year":"2015","journal-title":"Reprod. Domest. Anim."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/mrd.21117","article-title":"Generation of canine induced pluripotent stem cells by retroviral transduction and chemical inhibitors","volume":"77","author":"Shimada","year":"2009","journal-title":"Mol. Reprod. Dev."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Kim, S., Kim, B., Kim, J., Kim, D.-H., Lee, S., Lee, D.-S., and Lee, H. (2021). L-myc Gene Expression in Canine Fetal Fibroblasts Promotes Self-Renewal Capacity but Not Tumor Formation. Cells, 10.","DOI":"10.3390\/cells10081980"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1089\/scd.2012.0393","article-title":"Growth Requirements and Chromosomal Instability of Induced Pluripotent Stem Cells Generated from Adult Canine Fibroblasts","volume":"22","author":"Koh","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"32697","DOI":"10.1074\/jbc.M111.235739","article-title":"Preclinical Derivation and Imaging of Autologously Transplanted Canine Induced Pluripotent Stem Cells","volume":"286","author":"Lee","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"118701","DOI":"10.1016\/j.lfs.2020.118701","article-title":"Positioning canine induced pluripotent stem cells (iPSCs) in the reprogramming landscape of na\u00efve or primed state in comparison to mouse and human iPSCs","volume":"264","author":"Menon","year":"2020","journal-title":"Life Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.theriogenology.2017.01.013","article-title":"Generation of LIF-independent induced pluripotent stem cells from canine fetal fibroblasts","volume":"92","author":"Bressan","year":"2017","journal-title":"Theriogenology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1089\/scd.2011.0127","article-title":"Generation of Leukemia Inhibitory Factor and Basic Fibroblast Growth Factor-Dependent Induced Pluripotent Stem Cells from Canine Adult Somatic Cells","volume":"20","author":"Luo","year":"2011","journal-title":"Stem Cells Dev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1089\/scd.2011.0608","article-title":"Generation and Characterization of LIF-dependent Canine Induced Pluripotent Stem Cells from Adult Dermal Fibroblasts","volume":"21","author":"Whitworth","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1089\/scd.2018.0084","article-title":"Generation of Footprint-Free Canine Induced Pluripotent Stem Cells Using Auto-Erasable Sendai Virus Vector","volume":"27","author":"Tsukamoto","year":"2018","journal-title":"Stem Cells Dev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1089\/scd.2020.0084","article-title":"Efficient Reprogramming of Canine Peripheral Blood Mononuclear Cells into Induced Pluripotent Stem Cells","volume":"30","author":"Kimura","year":"2021","journal-title":"Stem Cells Dev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.scr.2017.11.010","article-title":"Safety and immune regulatory properties of canine induced pluripotent stem cell-derived mesenchymal stem cells","volume":"25","author":"Chow","year":"2017","journal-title":"Stem Cell Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/mrd.23349","article-title":"Generation of Footprint-Free Canine Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells Using Sendai Virus Vector","volume":"87","author":"Tsukamoto","year":"2020","journal-title":"Mol. Reprod. Dev."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Kim, M., Hwang, S.-U., Yoon, J.D., Jeong, Y.W., Kim, E., and Hyun, S.-H. (2020). Optimized Approaches for the Induction of Putative Canine Induced Pluripotent Stem Cells from Old Fibroblasts Using Synthetic RNAs. Animals, 10.","DOI":"10.3390\/ani10101848"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"102375","DOI":"10.1016\/j.scr.2021.102375","article-title":"Non-viral derivation of a transgene-free induced pluripotent stem cell line from a male beagle dog","volume":"53","author":"Yoshimatsu","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nbt.3070","article-title":"A comparison of non-integrating reprogramming methods","volume":"33","author":"Schlaeger","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Debowski, K., Warthemann, R., Lentes, J., Salinas-Riester, G., Dressel, R., Langenstroth, D., and Behr, R. (2015). Non-Viral Generation of Marmoset Monkey iPS Cells by a Six-Factor-in-One-Vector Approach. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118424"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.stemcr.2021.03.002","article-title":"Non-viral Induction of Transgene-free iPSCs from Somatic Fibroblasts of Multiple Mammalian Species","volume":"16","author":"Yoshimatsu","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"7641767","DOI":"10.1155\/2019\/7641767","article-title":"Generation of iPSCs by Nonintegrative RNA-Based Reprogramming Techniques: Benefits of Self-Replicating RNA versus Synthetic mRNA","volume":"2019","author":"Steinle","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1038\/sj.onc.1205400","article-title":"The proto-oncogene c-myc in hematopoietic development and leukemogenesis","volume":"21","author":"Hoffman","year":"2002","journal-title":"Oncogene"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1038\/sj.onc.1202592","article-title":"The proto-oncogene c-myc and apoptosis","volume":"17","author":"Hoffman","year":"1998","journal-title":"Oncogene"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S1097-2765(02)00520-8","article-title":"c-Myc Can Induce DNA Damage, Increase Reactive Oxygen Species, and Mitigate p53 Function: A Mechanism for Oncogene-Induced Genetic Instability","volume":"9","author":"Vafa","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nature10106","article-title":"Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1","volume":"474","author":"Maekawa","year":"2011","journal-title":"Nature"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1186\/s13287-020-02047-1","article-title":"Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases","volume":"11","author":"Tobias","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/age.12460","article-title":"The canine era: The rise of a biomedical model","volume":"47","author":"Leegwater","year":"2016","journal-title":"Anim. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s11897-020-00475-x","article-title":"New Insights in RBM20 Cardiomyopathy","volume":"17","author":"Lennermann","year":"2020","journal-title":"Curr. Hear. Fail. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Sacchetto, C., Vitiello, L., De Windt, L.J., Rampazzo, A., and Calore, M. (2020). Modeling Cardiovascular Diseases with hiPSC-Derived Cardiomyocytes in 2D and 3D Cultures. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093404"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/12\/13\/1679\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:40:45Z","timestamp":1760139645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/12\/13\/1679"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,29]]},"references-count":109,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ani12131679"],"URL":"https:\/\/doi.org\/10.3390\/ani12131679","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,29]]}}}