IDENTIFICATION OF THE LMO4 GENE ENCODING AN INTERACTION PARTNER OF THE LIM-BINDING PROTEIN LDB1 NLI1 - A CANDIDATE FOR DISPLACEMENT BY LMO PROTEINS IN T-CELL ACUTE-LEUKEMIA/

The T cell oncogenes LMO2 and LMO2 are activated by distinct chromosom al translocations in childhood T cell acute leukaemias. Transgenic mou se models of this disease demonstrate that enforced expression of Lmo1 and Lmo2 cause T cell leukaemias with long latency and that Lmo2 expr ession leads to an inhibition of the T cell differentiation programme, prior to overt disease. These functions appear to be partly mediated by interaction of LMO1 or LMO2 with the LIM-binding protein LDB1/NLI1. We have now identified a new member of the Lmo family, designated Lmo 4, via its interaction with Ldb1. Lmo4 is widely expressed in mouse ti ssues, including adult thymus (mainly CD4, CDS-double positive T cells ) and embryonic thymus (mainly CD4, CD8-double negative T cells). Thes e characteristics imply that Ldb1-Lmo4 interaction may function in the T cell developmental programme and that enforced expression of LMO1 o r LMO2 by chromosomal translocations or transgenesis may displace Lmo4 from this complex and thereby influence T cell differentiation prior to T cell tumour occurrence.