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c-Myb is required for progenitor cell homeostasis in colonic crypts

Malaterre, J. and Carpinelli, M. and Ernst, M. and Alexander, W. and Cooke, M. and Sutton, S. and Dworkin, S. and Heakth, J.K. and Frampton, J. and McArthur, G. and Clevers, J.C. and Hilton, D. and Mantamadiotis, Th. and Ramsay, R.G. (2007) c-Myb is required for progenitor cell homeostasis in colonic crypts. Proc Natl Acad Sci U S A., 104(10), 3829-3834. doi: 10.1073/pnas.0610055104. PMC_URL: http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1820669&blobtype=pdf.

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Abstract

The colonic crypt is the functional unit of the colon mucosa with a central role in ion and water reabsorption. Under steady-state conditions, the distal colonic crypt harbors a single stem cell at its base that gives rise to highly proliferative progenitor cells that differentiate into columnar, goblet, and endocrine cells. The role of c-Myb in crypt homeostasis has not been elucidated. Here we have studied three genetically distinct hypomorphic c-myb mutant mouse strains, all of which show reduced colonic crypt size. The mutations target the key domains of the transcription factor: the DNA binding, transactivation, and negative regulatory domains. In vivo proliferation and cell cycle marker studies suggest that these mice have a progenitor cell proliferation defect mediated in part by reduced Cyclin E1 expression. To independently assess the extent to which c-myb is required for colonic crypt homeostasis we also generated a novel tissue-specific mouse model to allow the deletion of c-myb in adult colon, and using these mice we show that c-Myb is required for crypt integrity, normal differentiation, and steady-state proliferation.

Item Type:Article
Additional Information:doi: 10.1073/pnas.0610055104. PMC_URL: http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1820669&blobtype=pdf
Institutes:Hubrecht Instituut
ID Code:3815
Deposited On:13 Feb 2009 17:14
Last Modified:10 Dec 2009 13:14

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