Abstract
The mammalian colon develops from a simple tube of undifferentiated cells into a complex, highly ordered organ, with a continuously self-renewing epithelial layer. We have previously described c-Myb expression in the epithelia of murine and human colon crypts and documented increased expression in colorectal adenocarcinoma cells. To investigate the role of c-Myb in colonic epithelium development, we have used embryos with a disrupted c-myb gene. Prior to the in utero death of these embryos at E15, we excised colon tissue and transplanted it under the kidney capsule of recipient mice to allow further development and cyto-differentiation. Compared to the colons of wildtype and heterozygous littermates, the c-myb homozygous knockout colon is highly irregular with a disordered epithelium and abnormal crypts. In addition, the expression of Bcl-2, a known target of c-Myb, is reduced and apoptosis is increased, indicating a critical requirement for c-Myb in normal colon development.
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Acknowledgements
We thank Lynne Trute for performing the β-catenin immunohistochemistry, Dr Andreas Strasser for reagents and Michele Cook and Jeon Cha for technical assistance. We also thank Drs Anne Thompson, Maree Overall and Grant McArthur for critical reading of the manuscript and David Bowtell and Joe Sambrook for instructive comments. This work was supported by a National Health and Medical Research Council Research Fellowship and the Anti-Cancer Council of Victoria, Australia.
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Zorbas, M., Sicurella, C., Bertoncello, I. et al. c-Myb is critical for murine colon development. Oncogene 18, 5821–5830 (1999). https://doi.org/10.1038/sj.onc.1202971
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DOI: https://doi.org/10.1038/sj.onc.1202971
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