integument
• in ex vivo assays, adhesion of ketatinocytes is increased in tamoxifen-treated cells relative to control cells
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• in ex vivo assays, migration of ketatinocytes is increased in tamoxifen-treated cells relative to control cells
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• after tamoxifen induction, the number and proliferation of hair follicles is increased compared to treated controls
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• in 6-8 week-old mutant mice after tamoxifen induction, the number and proliferation of hair follicles is increased compared to treated controls
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• suprabasal layer is multi-layered compared with single layer in controls
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neoplasm
• tamoxifen-treated mice show greater incidence and faster growth of DMBA/TPA-induced skin tumors compared with control animals (development by 12 weeks post treatment vs 15 weeks in controls; 80% of mice by 30 weeks vs 20% of controls); mutants demonstrate higher multiplicity (2 tumors/mouse vs 0.6/control) and greater size than controls
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digestive/alimentary system
• in tamoxifen-treated mutants, increased goblet cell proliferation is detected in the small intestine (inferred from increase in number and enlargement in size of Periodic acid-Schiff and Alcian Blue positive cells)
• neuroendocrine cells in the intestine are normal
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• mutants exhibit abnormal proliferation and differentiation of cell types in the small intestine including goblet, Paneth and stem cell/tuft cells; numbers are increased and loss of cell polarity and alterations in cell position are observed
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• increased numbers of Paneth cells are detected
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• Paneth cells are dislocated through crypt-villus axis
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cellular
• in tamoxifen-treated mutants, increased goblet cell proliferation is detected in the small intestine (inferred from increase in number and enlargement in size of Periodic acid-Schiff and Alcian Blue positive cells)
• neuroendocrine cells in the intestine are normal
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• in ex vivo assays, adhesion of ketatinocytes is increased in tamoxifen-treated cells relative to control cells
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• in ex vivo assays, migration of ketatinocytes is increased in tamoxifen-treated cells relative to control cells
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endocrine/exocrine glands
• increased numbers of Paneth cells are detected
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• Paneth cells are dislocated through crypt-villus axis
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homeostasis/metabolism
• tamoxifen-treated mice show greater incidence and faster growth of DMBA/TPA-induced skin tumors compared with control animals (development by 12 weeks post treatment vs 15 weeks in controls; 80% of mice by 30 weeks vs 20% of controls); mutants demonstrate higher multiplicity (2 tumors/mouse vs 0.6/control) and greater size than controls
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• after full-thickness wounds were introduced into the backs of tamoxifen-treated mutants and controls, wounds started to heal in control mice after 5 days with closure at 10 days whereas healing was significantly delayed in mutants; migration of cells toward the wound site occurs from both hair follicles and epidermal suprabasal layer
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