While tissue culture models of MondoA function are powerful, they do have their limitations. Therefore, we are also examining the function of Mondo orthologs in the mouse and in the nematode C. elegans. In the mouse system, we have generated a conditional allele of MondoA. We plan to knockout MondoA in the entire organism and in specific tissues to determine the role of MondoA in development and organismal energy homeostasis. In C. elegans, the "Myc"-like network is much simpler than in higher eukaryotes with clear Mondo, Mlx, Mad and Max orthologs. Surprisingly, there is no clear Myc ortholog in C. elegans. Our investigation of this simplified transcription factor network will afford us a better understanding of its biological role without the problems of genetic redundancy and compensation present when studying the network in higher eukaryotes.
