Developmental abnormalities in multiple proliferative tissues of ApcMin/+ mice

Germ‐line mutation of the Apc gene has been linked to familial adenomatous polyposis (FAP) that predisposes to colon cancer. ApcMin/+ 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 ApcMin/+ mice relative to C57BL/6 mice at 12 and 15 weeks of age. Vigorous splenic haematopoiesis in ApcMin/+ 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 ApcMin/+ mice at 15 weeks of age. Lymphoid depletion in ApcMin/+ mice was characterized by diminished numbers of splenic lymphoid follicles and small intestinal Peyer's patches. The ovaries of 12‐ and 15‐week‐old ApcMin/+ 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 ApcMin/+ 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.