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Molecular and Cellular Biology, December 2003, p. 9003-9013, Vol. 23, No. 24
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.24.9003-9013.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The LMO2 T-Cell Oncogene Is Activated via Chromosomal Translocations or Retroviral Insertion during Gene Therapy but Has No Mandatory Role in Normal T-Cell Development

Matthew P. McCormack, Alan Forster, Lesley Drynan, Richard Pannell, and Terence H. Rabbitts*

MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom

Received 16 July 2003/ Accepted 25 August 2003

The LMO2 gene encodes a LIM-only protein and is a target of chromosomal translocations in human T-cell leukemia. Recently, two X-SCID patients treated by gene therapy to rescue T-cell lymphopoiesis developed T-cell leukemias with retroviral insertion into the LMO2 gene causing clonal T-cell proliferation. In view of the specificity of LMO2 in T-cell tumorigenesis, we investigated a possible role for Lmo2 in T-lymphopoiesis, using conditional knockout of mouse Lmo2 with loxP-flanked Lmo2 and Cre recombinase alleles driven by the promoters of the lymphoid-specific genes Rag1, CD19, and Lck. While efficient deletion of Lmo2 was observed, even in the earliest detectable lymphoid cell progenitors of the bone marrow, there was no disturbance of lymphopoiesis in either T- or B-cell lineages, and in contrast to Lmo2 transgenic mice, there were normal distributions of CD4- CD8- thymocytes. We conclude that there is no mandatory role for LMO2 in lymphoid development, implying that its specific role in T-cell tumorigenesis results from a reprogramming of gene expression after enforced expression in T-cell precursors.

* Corresponding author. Mailing address: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom. Phone: 1223-402286. Fax: 1223-412178. E-mail: thr{at}mrc-lmb.cam.ac.uk.

Molecular and Cellular Biology, December 2003, p. 9003-9013, Vol. 23, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.24.9003-9013.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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