mortality/aging
• about 12% of older mice ranging in age from 20-56 weeks die or were sacrificed due to morbidity
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neoplasm
• neoplasms in multiple organs including the endometrium, liver, prostate, gastrointestinal tract, thyroid, and thymus
• tumors of the gastrointestinal epithelium develop in association with gut lymphoid tissue
• tumors of the endometrium, thyroid, prostate, and liver are not associated with lymphoid tissue and appear highly mitotic
• the tumors that cause morbidity include lymphomas, synchronous thyroid carcinoma, liver adenoma, poorly differentiated leukemia and teratoma
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• 3 of 8 males at 6-22 weeks of age display prostatic intraepithelial neoplasia; an additional 3 mice have foci of benign epithelial hyperplasia in the prostate
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• thyroid carcinoma
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• poorly differentiated leukemia
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• lymphomas develop in 7 of 256 mice that were clinically sick
• all mutants that develop lymphoma display diffuse microscopic infiltration of all organs by atypical immature lymphoid cells
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digestive/alimentary system
• intestinal polyps are seen in all mutants from 7 to 18 weeks of age; multiple polyps frequently cluster within a single region
• most polyps are lymphoid polyps with normal epithelium; the second most frequent type of polyp is lymphoid polyps with epithelial hyperplasia
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endocrine/exocrine glands
• 5 of the 7 mutants that develop lymphoma have an enlarged thymus
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• 3 of 20 mutants at 6-22 weeks of age display follicular or papillary noninvasive neoplasia of the thyroid and an additional 3 mice have atypical epithelial changes in the thyroid
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• 3 of 8 males at 6-22 weeks of age display prostatic intraepithelial neoplasia; an additional 3 mice have foci of benign epithelial hyperplasia in the prostate
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• thyroid carcinoma
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hematopoietic system
• 5 of the 7 mutants that develop lymphoma have an enlarged thymus
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• all mutants that develop lymphoma have splenomegaly
• by 50 weeks of age, all females and 45% of males have splenomegaly
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immune system
• 5 of the 7 mutants that develop lymphoma have an enlarged thymus
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• all mutants that develop lymphoma have splenomegaly
• by 50 weeks of age, all females and 45% of males have splenomegaly
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• in the hyperplastic lymph nodes and aggregates, follicular organization is blurred with mixing of the B and T cell regions
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• neoplastic hyperplasia of lymph nodes caused by a defect in apoptosis in B cells and macrophages
• expansion of the interfollicular areas, medullary cords, and residual follicular and paracortical hyperplasia composed of B, T, macrophage, and fibroblast cells
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reproductive system
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• 3 of 8 males at 6-22 weeks of age display prostatic intraepithelial neoplasia; an additional 3 mice have foci of benign epithelial hyperplasia in the prostate
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• 100% of females aged 18-39 weeks display multifocal endometrial complex atypical hyperplasia, a lesion that is a precursor of endometrial carcinoma
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growth/size/body
• all mutants that develop lymphoma have splenomegaly
• by 50 weeks of age, all females and 45% of males have splenomegaly
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liver/biliary system
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
Bannayan-Riley-Ruvalcaba syndrome | DOID:0050657 |
OMIM:158350 |
J:53065 | |
Cowden syndrome | DOID:6457 |
OMIM:PS158350 |
J:53065 |