PMID- 7753829
OWN - NLM
STAT- MEDLINE
DCOM- 19950616
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 92
IP  - 10
DP  - 1995 May 9
TI  - Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal 
      polyps in mice carrying a truncated Apc gene.
PG  - 4482-6
AB  - Mutations in the APC (adenomatous polyposis coli) gene appear to be responsible 
      for not only familial adenomatous polyposis but also many sporadic cases of 
      gastrointestinal cancers. Using homologous recombination in mouse embryonic stem 
      cells, we constructed mice that contained a mutant gene encoding a product 
      truncated at a 716 (Apc delta 716). Mendelian transmission of the gene caused 
      most homozygous mice to die in utero before day 8 of gestation. The heterozygotes 
      developed multiple polyps throughout the intestinal tract, mostly in the small 
      intestine. The earliest polyps arose multifocally during the third week after 
      birth, and new polyps continued to appear thereafter. Surprisingly, every nascent 
      polyp consisted of a microadenoma covered with a layer of the normal villous 
      epithelium. These microadenomas originated from single crypts by forming abnormal 
      outpockets into the inner (lacteal) side of the neighboring villi. We carefully 
      dissected such microadenomas from nascent polyps by peeling off the normal 
      epithelium and determined their genotype by PCR: all microadenomas had already 
      lost the wild-type Apc allele, whereas the mutant allele remained unchanged. 
      These results indicate that loss of heterozygosity followed by formation of 
      intravillous microadenomas is responsible for polyposis in Apc delta 716 
      intestinal mucosa. It is therefore unlikely that the truncated product interacts 
      directly with the wild-type protein and causes the microadenomas by a dominant 
      negative mechanism.
FAU - Oshima, M
AU  - Oshima M
AD  - Banyu Tsukuba Research Institute (Merck), Japan.
FAU - Oshima, H
AU  - Oshima H
FAU - Kitagawa, K
AU  - Kitagawa K
FAU - Kobayashi, M
AU  - Kobayashi M
FAU - Itakura, C
AU  - Itakura C
FAU - Taketo, M
AU  - Taketo M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Codon)
RN  - 0 (DNA Primers)
SB  - IM
GS  - APC
GS  - Apc
MH  - Adenoma/*genetics/pathology
MH  - Animals
MH  - Base Sequence
MH  - Blastocyst/metabolism
MH  - Chimera
MH  - *Chromosome Deletion
MH  - Codon
MH  - DNA Primers
MH  - Embryo, Mammalian
MH  - Epithelial Cells
MH  - Epithelium/pathology
MH  - Female
MH  - Fetal Death
MH  - *Gene Deletion
MH  - *Genes, APC
MH  - Humans
MH  - Intestinal Neoplasms/*genetics/pathology
MH  - Intestinal Polyps/*genetics/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Polymerase Chain Reaction
MH  - Pregnancy
MH  - Recombination, Genetic
MH  - Restriction Mapping
MH  - Stem Cells
PMC - PMC41968
EDAT- 1995/05/09 00:00
MHDA- 1995/05/09 00:01
PMCR- 1995/11/09
CRDT- 1995/05/09 00:00
PHST- 1995/05/09 00:00 [pubmed]
PHST- 1995/05/09 00:01 [medline]
PHST- 1995/05/09 00:00 [entrez]
PHST- 1995/11/09 00:00 [pmc-release]
AID - 10.1073/pnas.92.10.4482 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1995 May 9;92(10):4482-6. doi: 10.1073/pnas.92.10.4482.