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The B-cell CLL/lymphoma 11B gene <i>(BCL11B</i>) plays a crucial role in T-cell development, but its role in T-cell malignancies is still unclear. To study its role in the development of T-cell neoplasms, we generated an inducible <i>BCL11B</i> knockout in a murine T cell leukemia/lymphoma model. Mice, bearing human oncogenes TAL BHLH Transcription Factor 1 (<i>TAL1</i>; <i>SCL</i>) or LIM Domain Only 1 (<i>LMO1)</i>, responsible for T-cell acute lymphoblastic leukemia (T-ALL) development, were crossed with <i>BCL11B</i> floxed and with CRE-ER/lox mice. The mice with a single oncogene <i>BCL11B^flox/floxCRE</i>^tg/tg<i>TAL1</i>^tg or <i>BCL11B^flox/floxCRE</i>^tg/tg<i>LMO1</i>^tg were healthy, bred normally, and were used to maintain the mice in culture. When crossed with each other, >90% of the double transgenic mice <i>BCL11B^flox/floxCRE</i>^tg/tg<i>TAL1</i>^tg<i>LMO1</i>^tg, within 3 to 6 months after birth, spontaneously developed T-cell leukemia/lymphoma. Upon administration of synthetic estrogen (tamoxifen), which binds to the estrogen receptor and activates the Cre recombinase, the <i>BCL11B</i> gene was knocked out by excision of its fourth exon from the genome. The mouse model of inducible <i>BCL11B</i> knockout we generated can be used to study the role of this gene in cancer development and the potential therapeutic effect of <i>BCL11B</i> inhibition in T-cell leukemia and lymphoma.