Studying the importance of genetic factors in a desired cell type or tissue necessitates the use of precise genetic tools. With the introduction of bacteriophage Cre recombinase/loxP mediated DNA editing and promoter-specific Cre expression, it is feasible to generate conditional knockout @entity19 in which particular genes are disrupted in a cell type-specific manner in vivo. In cardiac myocytes, this is often achieved through a-myosin heavy chain promoter (aMyHC)-driven Cre expression in conjunction with a loxP-site flanked gene of interest. Recent studies in other cell types demonstrate @entity137 of Cre expression through induction of DNA damage. However, it is unclear to what extent the traditionally used aMyHC-Cre line [1] may exhibit @entity1370 . Further, the genotype of aMyHC-Cre(+/-) is not often included as a control group in cardiac myocyte-specific knockout studies. Here we present evidence that these aMyHC-Cre(+/-) @entity19 show molecular signs of @entity1370 by 3months of age and exhibit decreased cardiac function by 6months of age compared to wild-type littermates. Hearts from aMyHC-Cre(+/-) @entity19 also display evidence of @entity82 , @entity32 , and DNA damage. Interestingly, some of the early functional changes observed in aMyHC-Cre(+/-) @entity19 are sexually dimorphic. Given the high level of Cre recombinase expression resulting from expression from the aMyHC promoter, we asked if degenerate loxP-like sites naturally exist in the @entity19 genome and if so, whether they are affected by Cre in the absence of canonical loxP-sites. Using a novel bioinformatics search tool, we identified 619 loxP-like sites with 4 or less mismatches to the canonical loxP-site. 227 sites overlapped with annotated genes and 55 of these genes were expressed in cardiac muscle. Expression of ~26% of the 27 genes tested was disrupted in aMyHC-Cre(+/-) @entity19 indicating potential targeting by Cre. Taken together, these results highlight both the importance of using aMyHC-Cre @entity19 as controls in conditional knockout studies as well as the need for a less @entity1370 Cre driver for the field.

Prolonged Cre expression driven by the a-myosin heavy chain promoter can be XXXX .

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity1370 :: ('MESH:D066126', 'Disease') :: ['cardiotoxic', 'cardiotoxicity', 'cardiac toxicity']
@entity1370 :: (MESH:D066126,Disease) :: ['cardiotoxic']
