| First Author | Petrich BG | Year | 2003 |
| Journal | FASEB J | Volume | 17 |
| Issue | 6 | Pages | 749-51 |
| PubMed ID | 12594183 | Mgi Jnum | J:128410 |
| Mgi Id | MGI:3767036 | Doi | 10.1096/fj.02-0438fje |
| Citation | Petrich BG, et al. (2003) Temporal activation of c-Jun N-terminal kinase in adult transgenic heart via cre-loxP-mediated DNA recombination. FASEB J 17(6):749-51 |
| abstractText | 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. |
