Tumour suppressors: Timing will tell.

TheRb gene is known to put brakes on cell division, controlling cell numbers and thereby helping to prevent tumours from forming. Mutations that inactivate this 'tumour suppressor' gene are often seen in human cancers. One way in which researchers try to learn more about how the inactivation of particular genes contributes to cancer development is to mutate them in mice, and see what happens. But a problem with such mouse models is that they generally involve mutating the gene of interest in the germline, the tissue that produces eggs and sperm. Compensation could occur directly, if the back-up genes are simply upregulated or downregulated as appropriate as a direct result of Rb loss. Indirect mechanisms come into play abundantly during development of tumors, a distinct chromatin configuration is often fixed during development in a cell-type-specific fashion, and thereby imposed on all daughter cells.