This problem does not exist in our strategy because the inserted intron was deleted together with the majority part of the target operons via homologous recombination. Previously, the deleted genes in Clostridia, namely spo0A in C. acetobutylicum, as well as pyrF and pta in C. thermocellum, are all chromosomally-encoded. Our practice of deleting ctfAB provides the first example of targeted gene deletion in the acteoside megaplasmid of C. acetobutylicum, without affecting the megaplasmid stability, further demonstrating the effectiveness of this gene deletion strategy. In summary, the approach described above combines the advantage of the intron retrotransposition and homologous recombination. It eliminates the selection marker during the process of negative screening, which facilitates the genetic manipulation of multiple genes and operons in both chromosome and megaplasmid. To date, group II intron was used to Gelsemine inactivate genes in at least ten different bacterial species, for most of which targeted gene deletion is impossible. Therefore, the approach developed in this study has the potential to be applied for gene deletion in those species where first-step insertion via intron retrotransposition has been established. Numerous studies estimate that the oncogene HER2 is overexpressed in 20�C30% of primary breast cancers and this alteration correlates with poor prognosis. Further support for the involvement of HER2 in the initiation and progression of breast cancer comes from analysis of transgenic mice generated by targeting overexpression of activated neu to the mammary gland under the control of the murine mammary tumor virus promoter. Activated neu is a mutated form with valine instead of glutamic acid at residue 664 in the transmembrane domain. The mechanism of activation of 611-CTF involved the formation of constitutive homodimers by intermolecular disulfide bonding, consistent with our present findings. Studies to further evaluate the role of D16HER2 in tumor progression as well as its responsiveness to chemotherapy or targeted therapies for HER2-overexpressing breast carcinomas will benefit from the ability to noninvasively quantify tumor burden in live mice by measuring the activity of the reporter gene luciferase in our transgenic mouse model.