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Targeted disruption of c-myb in the chicken pre B-cell line DT40

Oncogene volume 21, pages 3076–3081 (2002)Cite this article

Abstract

The c-myb proto-oncogene is highly expressed in a wide variety of immature hematopoietic cells and plays a key role in the development of the hematopoietic system. c-myb and its retroviral counterpart v-myb encode transcription factors which have been implicated in the regulation of certain target genes. Targeting of c-myb in mouse embryonic stem cells by homologous recombination has provided clear evidence that c-myb is necessary for the proper development of most myeloid lineages of the hematopoietic system as well as of T-lymphocytes. Here we have explored the function of c-myb in the B-lymphoid lineage. We have used the chicken DT40 cells, a pre B-cell line which shows extremely high efficiencies of homologous recombination, as a model system to disrupt c-myb. DT40 cells lacking a functional c-myb gene are viable and show only minor perturbations of their growth parameters, indicating that c-myb is not an essential gene in these cells. We have used the c-myb null DT40 cells to analyse the expression of genes which have been previously been identified as myb target genes. Neither c-myc nor bcl-2, two putative myb targets, showed altered expression in the cells lacking c-myb. However, expression of the Pdcd4 gene, a myb target gene originally identified in a myelomonocytic cell line expressing a conditional form of v-myb, was diminished in the absence of c-myb. The c-myb knock-out cells described here should provide a useful model system for the identification and characterization of c-myb target genes in B-lymphoid cells.

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Acknowledgements

We thank D Wenning for excellent technical assistance, C Müller-Tidow for help with FACS analysis, J-M Buerstedde for cells, plasmids and advice, S Reed for the chicken bcl-2 cDNA and W Willenbrink for help with photography. This work was supported by a grant from the DFG (KL461/9-2) and by the Fonds der chemischen Industrie.

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  1. Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, D-48143 Münster, Germany

    Hartmut Appl & Karl-Heinz Klempnauer

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  1. Hartmut Appl
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  2. Karl-Heinz Klempnauer
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Correspondence to Karl-Heinz Klempnauer.

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Appl, H., Klempnauer, KH. Targeted disruption of c-myb in the chicken pre B-cell line DT40. Oncogene 21, 3076–3081 (2002). https://doi.org/10.1038/sj.onc.1205427

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