Generation and characterization of a Myh6-driven Cre knockin mouse line

Gene deletion by the Cre-Loxp system has facilitated functional studies of many critical genes in mice, offering important insights and allowing deeper understanding on the mechanisms underlying organ development and diseases, such as heart development and diseases. In this study, we generated a Myh6-Cre knockin mouse model by inserting the IRES-Cre-wpre-polyA cassette between the translational stop codon and the 3' untranslated region of the endogenous Myh6 gene. By crossing knockin mice with the Rosa26 reporter lines, we found that Myh6-Cre targeted cardiomyocytes at the embryonic and postnatal stages. In addition, we were able to inactivate the desmosome gene Desmoplakin (Dsp) by breeding Myh6-Cre mice with a conditional Dsp^flox knockout mouse line, which resulted in embryonic lethality during the mid-term pregnancy. These results suggest that the new Myh6-Cre mouse line can serve as a robust tool to dissect the distinct roles of genes involved in heart development and function.