TRANSFORMATION OF AXIAL SKELETON DUE TO OVEREXPRESSION OF BMI-1 IN TRANSGENIC MICE

THE oncogene bmi-1, which was originally found to be involved in B- and T-cell lymphoma formation(1-3) encodes a protein with a domain of homology to the Drosophila protein Posterior sex combs (Psc) and its relative Suppressor 2 of Zeste (Su(z)2) (refs 4 and 5), Psc is a member of the Polycomb-group gene family, which is required to maintain the repression of homeotic genes that regulate the identities of Drosophila segments(6). The possibility that bmi-1 may play a similar role in vertebrates was suggested by our previous finding(7) that mice lacking the bmi-1 gene show posterior transformations of the axial skeleton. Here we report that transgenic mice overexpressing Bmi-1 protein show the opposite phenotype, namely a dose-dependent anterior transformation of vertebral identity, The anterior expression boundary of the Hoxc-5 gene is shifted in the posterior direction, indicating that Bmi-1 is involved in the repression of Hox genes. We propose that Bmi-1 is a member of a vertebrate Polycomb complex that regulates segmental identity by repressing Hox genes throughout development.