• J. Malaterre
  • M. Carpinelli
  • M. Ernst
  • W. Alexander
  • M. Cooke
  • S. Sutton
  • S. Dworkin
  • J.K. Heakth
  • J. Frampton
  • G. McArthur
  • J.C. Clevers
  • D. Hilton
  • Th. Mantamadiotis
  • R.G. Ramsay
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.
Original languageEnglish
Pages (from-to)3829-3834
JournalProceedings of the National Academy of Sciences of the United States of America
StatePublished - 2007

ID: 445857