T-cell acute lymphoblastic lymphoma induced in transgenic mice by the RBTN1 and RBTN2 LIM-domain genes

Two members of the RBTN gene family, RBTN1/Ttg-1 and RBTN2/Ttg-2, were found by their association with T-cell tumour-specific chromosomal translocations and are thought to be involved in the aetiology of such T-cell tumours. Here a transgenic mouse model is described in which T-cell tumours are induced by the presence of RBTN1 and RBTN2 transgenes that direct expression in thymus-derived cells. The latency period for lymphoid tumour appearance is variable, and tumours occur in a small proportion of transgenic animals that develop T-cell acute lymphoblastic malignancies. No significant increase in the rate of tumour development was observed in RBTN1 transgenic mice infected with Moloney murine leukaemia virus, nor did tumours arise in mice bearing a construct in which RBTN1 was expressed from the insulin transcriptional promoter. These data, which provide formal proof of the oncogenic activity of these genes, suggest that aberrant expression of transcription factor genes, such as RBTN1 and RBTN2, functions in tumour aetiology by disturbing some aspect of T-cell differentiation.