Analysis Tools
mortality/aging
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• by 6 months of age, 90% of the mutant mice die or are humanely killed because of their ill health
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neoplasm
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• all mutant mice develop thymic tumors
• thymic tumors have high CD8 expression, with variable CD4 expression
• high expression of heat-stable antigen (CD24) but do not have surface expression of the TCR beta-chain (TCRbeta)
• most but not all tumors have intracellular expression of TCRbeta
• Notch1 mutation is present in a minority of tumors and affected mainly the heterodimerization domain (25%) rather than the PEST domain (8%)
• primary tumor cells cultured in vitro are Notch1 dependent and killed by Zfp36l1 re-expression
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• development of T cell acute lymphoblastic leukemia
• circulating lymphoblasts in peripheral blood
• tumor cells in thymus, spleen, lymph node and bone marrow
• predominantly oligoclonal
• corresponding to the CD8+ immature single-positive (CD8iSP) and double-positive (DP) stages of thymic development
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immune system
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• perturbed thymopoiesis before tumor development
• thymic atrophy at 3 and 8 weeks of age
• gradual expansion of the CD8iSP population (CD8+CD4_CD24hi, membrane TCRbeta negative) in both proportion and absolute number by 13 weeks
• less progression from double-negative 2 (DN2) (CD44+CD25+) to DN3 (CD44_CD25+)
• decreased proportion of DN thymocytes with icTCRbeta expression
• only 30% of CD8iSP cells and 90% of DP cells have icTCRbeta expression
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• thymic atrophy at 3 and 8 weeks of age
• total thymic cellularity is approximately 50% that of control mice
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• many mutant mice have splenomegaly
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• many mutant mice have lymphadenopathy
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cellular
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• increased cellular proliferation by EdU staining in thymic populations from mice aged 5 and 10 weeks old
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hematopoietic system
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• perturbed thymopoiesis before tumor development
• thymic atrophy at 3 and 8 weeks of age
• gradual expansion of the CD8iSP population (CD8+CD4_CD24hi, membrane TCRbeta negative) in both proportion and absolute number by 13 weeks
• less progression from double-negative 2 (DN2) (CD44+CD25+) to DN3 (CD44_CD25+)
• decreased proportion of DN thymocytes with icTCRbeta expression
• only 30% of CD8iSP cells and 90% of DP cells have icTCRbeta expression
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• thymic atrophy at 3 and 8 weeks of age
• total thymic cellularity is approximately 50% that of control mice
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• many mutant mice have splenomegaly
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endocrine/exocrine glands
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• perturbed thymopoiesis before tumor development
• thymic atrophy at 3 and 8 weeks of age
• gradual expansion of the CD8iSP population (CD8+CD4_CD24hi, membrane TCRbeta negative) in both proportion and absolute number by 13 weeks
• less progression from double-negative 2 (DN2) (CD44+CD25+) to DN3 (CD44_CD25+)
• decreased proportion of DN thymocytes with icTCRbeta expression
• only 30% of CD8iSP cells and 90% of DP cells have icTCRbeta expression
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• thymic atrophy at 3 and 8 weeks of age
• total thymic cellularity is approximately 50% that of control mice
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• all mutant mice develop thymic tumors
• thymic tumors have high CD8 expression, with variable CD4 expression
• high expression of heat-stable antigen (CD24) but do not have surface expression of the TCR beta-chain (TCRbeta)
• most but not all tumors have intracellular expression of TCRbeta
• Notch1 mutation is present in a minority of tumors and affected mainly the heterodimerization domain (25%) rather than the PEST domain (8%)
• primary tumor cells cultured in vitro are Notch1 dependent and killed by Zfp36l1 re-expression
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growth/size/body
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• many mutant mice have splenomegaly
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| acute lymphoblastic leukemia | DOID:9952 |
OMIM:247640 OMIM:613065 |
J:162388 | |
