{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:03:20Z","timestamp":1790683400512,"version":"4.1.0"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T00:00:00Z","timestamp":1553558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["220996-151999"],"award-info":[{"award-number":["220996-151999"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The genetic modification of the mouse genome using the cre-lox system has been an invaluable tool in deciphering gene and protein function in a temporal and\/or spatial manner. However, it has its pitfalls, as researchers have shown that the unregulated expression of cre recombinase can cause DNA damage, the consequences of which can be very detrimental to mouse health. Previously published literature on the most utilized cardiac-specific cre, \u03b1MHC-cre, mouse model exhibited a nonlethal hypertrophic cardiomyopathy (HCM) with aging. However, using the same \u03b1MHC-cre mice, we observed a cardiac pathology, resulting in complete lethality by 11 months of age. Echocardiography and histology revealed that the \u03b1MHC-cre mice were displaying symptoms of dilated cardiomyopathy (DCM) by seven months of age, which ultimately led to their demise in the absence of any HCM at any age. Molecular analysis showed that this phenotype was associated with the DNA damage response through the downregulation of activated p38 and increased expression of JNK, p53, and Bax, known inducers of myocyte death resulting in fibrosis. Our data urges strong caution when interpreting the phenotypic impact of gene responses using \u03b1MHC-cre mice, since a lethal DCM was induced by the cre driver in an age-dependent manner in this commonly utilized model system.<\/jats:p>","DOI":"10.3390\/molecules24061189","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T05:03:12Z","timestamp":1553662992000},"page":"1189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Cardiac-Specific Cre Induces Age-Dependent Dilated Cardiomyopathy (DCM) in Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1820-0919","authenticated-orcid":false,"given":"Taha","family":"Rehmani","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysoon","family":"Salih","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balwant S.","family":"Tuana","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,26]]},"reference":[{"key":"ref_1","first-page":"163","article-title":"Transgenic animal models in biomedical research","volume":"360","author":"Houdebine","year":"2007","journal-title":"Methods Mol. 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