| First Author | Smith RW | Year | 2012 |
| Journal | Am J Respir Cell Mol Biol | Volume | 46 |
| Issue | 1 | Pages | 115-24 |
| PubMed ID | 21852686 | Mgi Jnum | J:191911 |
| Mgi Id | MGI:5463549 | Doi | 10.1165/rcmb.2011-0099OC |
| Citation | Smith RW, et al. (2012) Roles for beta-catenin and doxycycline in the regulation of respiratory epithelial cell frequency and function. Am J Respir Cell Mol Biol 46(1):115-24 |
| abstractText | The expression of beta-catenin-dependent genes can be increased through the Cre recombinase (Cre)-mediated elimination of the exon 3-encoded sequence. This mutant beta-catenin is termed DE3, and promotes the expression of beta-catenin-dependent genes. Our previous study used the DE3 model to demonstrate that persistent beta-catenin activity inhibited bronchiolar Clara-to-ciliated cell differentiation. The present study was designed to evaluate the roles of beta-catenin in regulating the tracheal progenitor cell hierarchy. However, initial experiments demonstrated that the tetracycline-responsive element-Cre transgene (TRE-Cre) was active in the absence of a reverse tetracycline transactivator driver or inducer, doxycycline (Dox). This spurious TRE-Cre transgene activity was not detected using the ROSA26-floxed STOP-LacZ reporter. To determine if the phenotype was a consequence of genotype or treatment with Dox, tracheal and lung specimens were evaluated using quantitative histomorphometric techniques. Analyses of uninduced mice demonstrated a significant effect of genotype on tracheal epithelial cell mass, involving basal, Clara-like cell types. The bronchial and bronchiolar Clara cell mass was also decreased. Paradoxically, an effect on ciliated cell mass was not detected. Activation of the beta-catenin reporter transgene TOPGal demonstrated that beta-catenin-dependent gene expression led to the genotype-dependent tracheal and bronchiolar phenotype. Comparative analyses of wild-type or keratin 14-rtTA(+/0)/TRE-cre(+/0)/DE3(+/+) mice receiving standard or Dox chow demonstrated an effect of treatment with Dox on basal, Clara-like, and Clara cell masses. We discuss these results in terms of cautionary notes and with regard to alterations of progenitor cell hierarchies in response to low-level injury. |
