Temporal activation of c-Jun N-terminal kinase in adult transgenic heart via cre-loxP-mediated DNA recombination.

Journal Article (Journal Article)

Using a cre-loxP-mediated gene-switch approach, we achieved targeted JNK activation in adult hearts. A transgenic model is established carrying a floxed gene-switch construct that directs GFP marker gene expression in the absence of DNA recombination between two loxP sites. A tamoxifen-inducible Cre recombinase was introduced in the transgenic heart by breeding with previously established Mer-Cre-Mer transgenic mice. Upon tamoxifen administration in double transgenic adult animals, cre-loxP-mediated DNA recombination efficiently switches "off" the loxP-flanked GFP expression unit in cardiomyocytes and switches "on" the expression of the target gene, MKK7D, a constitutively activated upstream activator of c-Jun N-terminal kinases (JNK). Expression of MKK7D in adult hearts resulted in significant activation of JNK activities and causes progressive cardiomyopathy in transgenic animals. This unique animal model of cardiac-specific and temporally regulated JNK activation will provide a powerful tool to investigate the functional role of the JNK pathway in the development of heart failure. Our data also demonstrated that the inducible gene-switch approach reported here may also be applicable in other studies to achieve efficient, tissue-specific, and temporally regulated genetic manipulation in intact animals.

Full Text

Duke Authors

Cited Authors

  • Petrich, BG; Molkentin, JD; Wang, Y

Published Date

  • April 2003

Published In

Volume / Issue

  • 17 / 6

Start / End Page

  • 749 - 751

PubMed ID

  • 12594183

Electronic International Standard Serial Number (EISSN)

  • 1530-6860

Digital Object Identifier (DOI)

  • 10.1096/fj.02-0438fje

Language

  • eng

Conference Location

  • United States