c-Myb is required for progenitor cell homeostasis in colonic crypts
- Malaterre, J; Carpinelli, M; Ernst, M; Alexander, W; Cooke, M; Sutton, S; Dworkin, S; Heath, JK; Frampton, J; McArthur, G; Clevers, H; Hilton, D; Mantamadiotis, T; Ramsay, RG;
Publication Year 2007-03-06, Volume 104, Issue #10, Page 3829-3834
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- 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.
- NATL ACAD SCIENCES
- GASTROINTESTINAL EPITHELIUM; EXPRESSION; DIFFERENTIATION; MICE; GENE; PROLIFERATION; HEMATOPOIESIS; DISEASE; MOUSE; DEATH
- Publisher's Version
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Creation Date: 2007-03-06 12:00:00Last Modified: 0001-01-01 12:00:00