Developmental abnormalities in multiple proliferative tissues of Apc(Min/+) mice.
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.
You
Shaojin
S
Center for Colon Cancer Research, Dorn Research Institute, WJB Dorn Veterans Affairs Medical Center (151), Columbia, SC 29209, USA.
Ohmori
Masami
M
Peña
Maria Marjorette O
MM
Nassri
Basel
B
Quiton
Jovelyn
J
Al-Assad
Ziad A
ZA
Liu
Lucy
L
Wood
Patricia A
PA
Berger
Sondra H
SH
Liu
Zhijian
Z
Wyatt
Michael D
MD
Price
Robert L
RL
Berger
Franklin G
FG
Hrushesky
William J M
WJ
D011125:Adenomatous Polyposis Coli / Q000473:pathology*; D000818:Animals; D005260:Female; D017491:Genes, APC; D018095:Germ-Line Mutation; D006410:Hematopoiesis; D007413:Intestinal Mucosa / Q000473:pathology*; D007422:Intestines / Q000473:pathology*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D023421:Models, Animal; D010053:Ovary / Q000473:pathology; D013737:Testis / Q000473:pathology