PMID- 9697701
OWN - NLM
STAT- MEDLINE
DCOM- 19980901
LR  - 20220321
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 19
IP  - 4
DP  - 1998 Aug
TI  - Depletion of epithelial stem-cell compartments in the small intestine of mice 
      lacking Tcf-4.
PG  - 379-83
AB  - Mutations of the genes encoding APC or beta-catenin in colon carcinoma induce the 
      constitutive formation of nuclear beta-catenin/Tcf-4 complexes, resulting in 
      activated transcription of Tcf target genes. To study the physiological role of 
      Tcf-4 (which is encoded by the Tcf7/2 gene), we disrupted Tcf7/2 by homologous 
      recombination. Tcf7/2-/- mice die shortly after birth. A single histopathological 
      abnormality was observed. An apparently normal transition of intestinal endoderm 
      into epithelium occurred at approximately embryonic day (E) 14.5. However, no 
      proliferative compartments were maintained in the prospective crypt regions 
      between the villi. As a consequence, the neonatal epithelium was composed 
      entirely of differentiated, non-dividing villus cells. We conclude that the 
      genetic program controlled by Tcf-4 maintains the crypt stem cells of the small 
      intestine. The constitutive activity of Tcf-4 in APC-deficient human epithelial 
      cells may contribute to their malignant transformation by maintaining stem-cell 
      characteristics.
FAU - Korinek, V
AU  - Korinek V
AD  - Department of Immunology, University Hospital, Utrecht, The Netherlands.
FAU - Barker, N
AU  - Barker N
FAU - Moerer, P
AU  - Moerer P
FAU - van Donselaar, E
AU  - van Donselaar E
FAU - Huls, G
AU  - Huls G
FAU - Peters, P J
AU  - Peters PJ
FAU - Clevers, H
AU  - Clevers H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (TCF Transcription Factors)
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Tcf7l2 protein, mouse)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Endoderm/pathology
MH  - Epithelial Cells/cytology
MH  - Intestine, Small/*cytology/embryology
MH  - Mice
MH  - Mice, Knockout
MH  - Microvilli/ultrastructure
MH  - Stem Cells/*cytology
MH  - TCF Transcription Factors
MH  - Transcription Factor 7-Like 2 Protein
MH  - Transcription Factors/analysis/genetics/*physiology
EDAT- 1998/08/11 02:49
MHDA- 2001/03/23 10:01
CRDT- 1998/08/11 02:49
PHST- 1998/08/11 02:49 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1998/08/11 02:49 [entrez]
AID - 10.1038/1270 [doi]
PST - ppublish
SO  - Nat Genet. 1998 Aug;19(4):379-83. doi: 10.1038/1270.