Loss- and gain-of-function mutations show a Polycomb group function for Ring1A in mice

The products of the Polycomb group (PcG) of genes act as transcriptional re pressors involved in the maintenance of homeotic gene expression patterns t hroughout development, from flies to mice. Biochemical and molecular eviden ce suggests that the mouse Ring1A gene is a member of the PcG of genes. How ever, genetic evidence is needed to establish PcG function for Ring1A, sinc e contrary to all other murine PcG genes, there is no known Drosophila PcG gene encoding a homolog of the Ring1A protein. To study Ring1A function we have generated a mouse line lacking Ring1A and mouse lines overexpressing R ing1A, Both Ring1A(-/-) and Ring1A(+/-) mice show anterior transformations and other abnormalities of the axial skeleton, which indicates an unusual s ensitivity of axial skeleton patterning to Ring1A gene dosage, Ectopic expr ession of Ring1A also results in dose-dependent anterior transformations of vertebral identity, many of which, interestingly, are shared by Ring1A(-/- ) mice. In contrast, the alterations of Hox gene expression observed in bot h type of mutant mice are subtle and involve a reduced number of Hox genes. Taken together, these results provide genetic evidence for a PcG function of the mouse Ring1A gene.