Samenvatting
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.
Originele taal-2 | Engels |
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Pagina's (van-tot) | 3829-3834 |
Aantal pagina's | 6 |
Tijdschrift | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 104 |
Nummer van het tijdschrift | 10 |
DOI's | |
Status | Gepubliceerd - 6 mrt. 2007 |
Extern gepubliceerd | Ja |