HIGH-INCIDENCE OF T-CELL TUMORS IN E2A-NULL MICE AND E2A ID1 DOUBLE-KNOCKOUT MICE/

The basic-helix-loop-helix (bHLH) proteins encoded by the E2A gene are broadly expressed transcription regulators which function through bin ding to the E-box enhancer sequences. The DNA binding activities of E2 A proteins are directly inhibited upon dimerization with the Idl gene product. It has been shown that disruption of the E2A gene leads to a complete block in B-lymphocyte development and a high frequency of neo natal death. We report here that nearly half of the surviving E2A-null mice develop acute T-cell lymphoma between 3 to 10 months of age. We further show that disruption of the Id1 gene improves the chance of po stnatal survival of E2A-null mice, indicating that Idl is a canonical negative regulator of E2A and that the unbalanced ratio of E2A to Idl may contribute to the postnatal death of the E2A-null mice. However, t he E24/Id1 double-knockout mice still develop T-cell tumors once they reach the age of 3 months. This result suggests that E2A may be essent ial for maintaining the homeostasis of T lymphocytes during their cons tant renewal in adult life.