Analysis Tools
mortality/aging
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• mice administered a single low dose (4 mg/kg) of tamoxifen to induce cre recombination survive 2 months and then die with multiple abnormalities
• tamoxifen-administered mice treated with rapamycin show improved survival but no improvement in organ abnormalities such as liver and spleen disorganization with aberrant vascularization
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• mice start to rapidly die after 40 mg/kg tamoxifen administration, with 50% of mortality at day 9
• tamoxifen-administered mice treated with BYL719 are alive after 40 days, however interruption of BYL719 treatment 40 days after tamoxifen-administration leads to rapid death
• tamoxifen-administered mice treated with rapamycin show improved survival but no improvement in organ abnormalities such as liver and spleen disorganization with aberrant vascularization
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growth/size/body
kidney cyst
(
J:264410
)
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• kidney cysts in tamoxifen-administered mice
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• organomegaly is seen in mice administered a single low dose of tamoxifen
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cardiovascular system
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• vessel abnormalities in tamoxifen-administered mice
• tamoxifen-administered mice treated with BYL719 show normal vessels
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• ecstatic venous channels with a thin endothelial cell lining, surrounded by sparse, erratically distributed vascular smooth muscle cells and a disorganized extracellular matrix are seen in mice administered a low dose of tamoxifen
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• severe vessel dilation in tamoxifen-administered mice
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• intra-abdominal hemorrhages in tamoxifen-administered mice
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• hepatic hemorrhages in tamoxifen-administered mice
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cellular
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• high number of proliferating cells in affected organs of tamoxifen-administered mice
• however, no changes in apoptosis are seen
• tamoxifen-administered mice treated with BYL719 show a reduction in proliferation
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hematopoietic system
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• loss of spleen microarchitecture integrity in tamoxifen-administered mice
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immune system
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• loss of spleen microarchitecture integrity in tamoxifen-administered mice
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• expansion of lymphatic vessels in tamoxifen-administered mice
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limbs/digits/tail
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• mice administered a single low dose of tamoxifen progressively develop asymmetrical overgrowth of extremities, disseminated voluminous tumors and subcutaneous vascular abnormalities
• low-dose tamoxifen administered mice treated with BYL719 show improvement of the overgrowth of extremities, however, withdrawal of BYL719 leads to the development of asymmetric extremity hypertrophy within 4 weeks
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liver/biliary system
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• hepatic hemorrhages in tamoxifen-administered mice
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• severe liver steatosis with vessel disorganization in tamoxifen-administered mice
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muscle
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• muscle hypertrophy in tamoxifen-administered mice
• mice treated with BYL719 7 days after cre induction show improved muscle hypertrophy
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neoplasm
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• low dose tamoxifen-administered mice develop tumors that are lipomatous tumors and severe vascular lesions mixing venous and arterial vessels
• low-dose tamoxifen administered mice treated with BYL719 show reduced and disappearance of visible tumors within 2 weeks
• withdrawal of BYL719 from the low-dose tamoxifen administered mice leads to recurrence of tumors
• low-dose tamoxifen-administered mice treated with rapamycin show no effect on tumor growth
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renal/urinary system
kidney cyst
(
J:264410
)
|
• kidney cysts in tamoxifen-administered mice
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• fibrosis of the kidney with aberrant vessels in tamoxifen-administered mice
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skeleton
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• scoliosis in tamoxifen-administered mice
• mice treated with BYL719 7 days after cre induction show improved scoliosis
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CLOVES syndrome | DOID:0080351 |
OMIM:612918 |
J:264410 | |
