ESCI award lecture: from a little mouse to rationale medicine for bone loss.

Completion of the human genome is one of the many significant milestones in the new era of systems biology. The current phase of genomic studies is focused upon parsing this new found genetic data with respect to scientific interest, and economic and health impact applications. As the sequences are now available and whole genome single nucleotide polymorphism maps for multiple human diseases will be available with the advent of modern genomics, the big challenge is to determine the function of these genes in the context of the entire organism. The emphasis is therefore on functional genomic analysis that represents the new front-line and limiting factor for realizing potential benefits of genome-based science. Defined gene targeting has been proven to be particularly useful as loss of expression mutants can reveal essential functions of molecules and the pathogenesis of disease. Using gene-targeted mice, my group has over the years identified genes that control heart and lung functions; apoptosis; lymphocyte activation; cancer; pain; diabetes; fertility or wound healing . In this study, I would like to review our work on RANKL in more detail.