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Int J Exp
Pathol. 2006 Jun;87(3):227-36.
Developmental abnormalities in multiple proliferative tissues of
Apc(Min/+) mice.
You S, Ohmori M, Pena MM, Nassri B, Quiton
J, Al-Assad ZA, Liu L, Wood PA, Berger
SH, Liu Z, Wyatt MD, Price RL, Berger FG,
Hrushesky WJ.
Center for Colon Cancer Research, Dorn Research Institute, WJB Dorn
Veterans Affairs Medical Center (151), Columbia, SC 29209, USA.
Germ-line
mutation of the Apc gene has been linked to familial adenomatous
polyposis (FAP) that predisposes to colon cancer. Apc(Min/+) mice,
heterozygous for the Apc gene mutation, progressively develop small
intestinal tumours in a manner that is analogous to that observed in
the colon of patients with FAP (Su et al. 1992; Fodde et al. 1994;
Moser et al. 1995). We have studied the effects of Apc gene mutation on
murine intestinal and extra-intestinal, proliferatively active tissues.
We have contrasted the histology to that of the age- and sex-matched
wild-type C57BL/6 mice. Histological assessment of the normal appearing
intestinal mucosa demonstrates minimal change in size of crypts. In
contrast, villi are longer in the ileum of Apc(Min/+) mice relative to
C57BL/6 mice at 12 and 15 weeks of age. Vigorous splenic haematopoiesis
in Apc(Min/+) mice was seen at 12 and 15 weeks of age, as reflected by
marked splenomegaly, increased splenic haematopoietic cells and
megakaryocytes. Peripheral blood counts, however, did not differ
between C57BL/6 and Apc(Min/+) mice at 15 weeks of age. Lymphoid
depletion in Apc(Min/+) mice was characterized by diminished numbers of
splenic lymphoid follicles and small intestinal Peyer's patches. The
ovaries of 12- and 15-week-old Apc(Min/+) mice exhibited increased
numbers of atretic follicles, and estrous cycling by serial vaginal
smears showed tendency of elongation in the mutant mice during these
age ranges. The testicles of 10-week-old Apc(Min/+) mice showed
increased numbers of underdeveloped seminiferous tubules. Collectively,
these data suggest that, in addition to its obvious effects upon
intestinal adenoma formation, Apc gene mutation causes impairment of
developmental and apparent differentiation blockade in proliferative
tissues, including those of the haematopoietic system, lymphoid and
reproductive tract.
PMID: 16709231 [PubMed - in process]
PubMed
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