A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors.

Abstract

ABSTRACT

Mouse models for colorectal cancer

“…These heterozygotes have a longer lifespan of a year or more, perhaps because of the fact that, on average, each mouse develops only 3 ± 5 adenomas/carcinomas of the small intestine . In one case we documented liver metastasis of the gastrointestinal tumor (Fodde et al, 1994). The Apc1638N animals also display extracolonic manifestations that resemble those of human FAP or Gardners syndrome.…”

“…In an attempt to mimic human gene mutations, we generated a mutant mouse, designated Apc1638N (Fodde et al, 1994). In this mouse line, a neomycin expression cassette was inserted at the position corresponding to codon 1638 of the Apc gene in the reverse transcriptional orientation.…”

“…This mutation results in an unstable 182-kD truncated protein that is di cult to detect by Western blot analysis. Apc1638N heterozygotes progressively develop colonic aberrant crypt foci and polyps and adenomas and carcinomas in the small intestine (Fodde et al, 1994). These heterozygotes have a longer lifespan of a year or more, perhaps because of the fact that, on average, each mouse develops only 3 ± 5 adenomas/carcinomas of the small intestine .…”

Heterogeneity of Jagged1 expression in human and mouse intestinal tumors: implications for targeting Notch signaling

“…Apc Min/ þ (Moser et al, 1990) and Apc 1638N/ þ (Fodde et al, 1994) mice on C57BL/6 background were treated according to animal protocols approved by the Animal Care and Use Committee at Montefiore Medical Center and the Albert Einstein College of Medicine. Small and large intestine were removed immediately after killing the mice at 5 or 8 months of age (Apc Min/ þ and Apc 1638N/ þ , respectively), flushed gently with cold phosphate-buffered saline, opened longitudinally and inspected with a dissection microscope.…”

Cell-type specific MyD88 signaling is required for intestinal tumor initiation and progression to malignancy

“…1C). Interbreeding of Myd88 LSL/LSL , Myd88 IEC and Myd88 MYEL animals with the genetic model Apc 1638N/+ for colorectal cancer 19 enabled the analysis of MyD88-mediated signaling during tumor formation. At 12 months of age, all examined Apc 1638N/+ mice developed intestinal tumors with an average of 3.4 ± 1.9 tumors per animal, whereas wildtype controls remained tumor-free.…”