Loss of Rho function in the thymus is accompanied by the development of thymic lymphoma

In situ studies in model cell lines have implicated the GTPase Rho in the c ontrol of diverse cellular responses including the control of the actin cyt oskeleton and the regulation of cell cycle progression. It is also reported that the transformation of fibroblasts via oncogenic Ras requires intact R ho signalling. An invaluable tool used to investigate Rho function is the b acterial toxin C3 transferase derived from Clostridium hotulinum. C3 transf erase ribosylates Rho in its effector domain thereby abolishing interaction with downstream effecters. We have previously reported the use of C3 trans ferase under the control of the thymocyte specific Ick promoter to explore the role of Rho in T cell biology. Strikingly, Ick-C3 mice develop aggressi ve malignant thymic lymphoblastic lymphomas between 4 and 8 months of age. These studies reveal that loss of Rho function is associated with prediposi tion to lymphoid cell transformation. Inhibition of Rho function has been s uggested as a therapeutic strategy for treatment of Ras-transformed tumours , The development of lymphomas in mice devoid of functional Rho in their T cell compartment shows that such a strategy would need to be used with caut ion.