In this grant, we propose to develop mice that have the Deleted in liver cancer (Dlc) Tumour Suppressor genes inactivated in specific tissues to better understand the function these genes play in tumour formation in whole animals. To carry out these experiments, we build small DNA molecules in test tubes that contain pieces of the Dlc genes. We then place these small pieces of DNA into mouse embryo cells where they combine with the normal gene located on the chromosomes. We can then make mice using these altered embryonic stem cells and target inactivation of this Dlc gene to a specific organ such as the liver. By using these mice that have inactivated Dlc genes, we aim to learn whether these genes can cooperate with other cancer causing genes to form more aggressive tumours, to better model what happens in patients' tumours.