| QM, a novel gene which was originally identified as a putative tumor suppressor gene, has since been cloned from species encompassing members of the plant, animal, and fungal kingdoms. Sequence comparison indicates that QM has been highly conserved throughout eukaryotic evolution. QM is a member of a multigene family in both mouse and man, is expressed in a broad range of tissues, and is downregulated during adipocyte differentiation. Jif-1, a chicken homolog of QM, has been reported to interact with the protooncogene c-Jun, and to inhibit transactivation of AP-1 regulated genes in vitro. Furthermore, disruption of the yeast QM homolog is lethal. Although these studies suggest that the QM gene product plays an important role within the cell, the precise role of QM has remained elusive. In this study, the murine system has been utilized to elucidate the role of the QM gene product. Four independent, but interrelated approaches have been used. First, the murine QM gene was cloned, characterized, and the chromosomal localization determined. Second, a thorough analysis of the pattern of QM expression during mouse development was undertaken, using the techniques of whole mount in situ hybridization and whole mount immunohistochemistry, in combination with conventional immunohistochemical analysis of tissue sections. Third, human QM was overexpressed within proliferating basal keratinocytes of the epidermis of transgenic mice, using the keratin 14 promoter. Fourth, gene-targeted disruption of QM within embryonic stem cells was pursued in order to determine the requirement for the QM gene product during embryogenesis. These studies have indicated that the general structure of murine QM is similar to the human QM gene, and like human QM, maps to the X chromosome. QM is expressed in numerous embryonic tissues, and is differentially expressed throughout the embryo. The cytoplasmic localization of QM is consistent with its reported association within ribosomes, and inconsistent with its previously hypothesized function as a modulator of the nuclear protooncogene c-Jun. While the QM gene product does not appear to be intrinsically required for protein synthesis, these studies have indicated that QM provides an essential role within the normal cell. |
