{"id":"369c3027-8c08-5e07-9065-2b7a6039e204","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-inactivation-causes-mouse-malignancy","predicate":"loss_increases","statement":"Inactivating Tet2 in mouse perturbed both early and late haematopoiesis in a cell-autonomous manner, gave the cells a competitive advantage, and eventually led to the development of haematological malignancies.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"ccfbd575-86a5-5944-ba79-9d1a74fe3423","mechanism_event_label":"Inactivating Tet2 in mouse perturbed both early and late haematopoiesis in a cell-autonomous manner, gave the cells a competitive advantage, and eventually led to the development of haematological malignancies.","subject":{"id":"36d7160b-6534-58a6-a0df-55bcde8e740c","slug":"tet2-mouse","display_name":"Mouse Tet2","entity_type_key":"protein"},"object":{"id":"9b0171b8-cdcd-5949-9d70-49ce9cac555d","slug":"mouse-haematological-malignancy","display_name":"Haematological malignancy in mice","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ccfbd575-86a5-5944-ba79-9d1a74fe3423","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-inactivation-causes-mouse-malignancy-event","event_type":"observed_relationship","label":"Inactivating Tet2 in mouse perturbed both early and late haematopoiesis in a cell-autonomous manner, gave the cells a competitive advantage, and eventually led to the development of haematological malignancies.","description":"A second group's mice also developed blood cancers after Tet2 was switched off.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"36d7160b-6534-58a6-a0df-55bcde8e740c","slug":"tet2-mouse","display_name":"Mouse Tet2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9b0171b8-cdcd-5949-9d70-49ce9cac555d","slug":"mouse-haematological-malignancy","display_name":"Haematological malignancy in mice","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"duration","value_text":"In vivo, to malignancy","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Tet2-inactivated mice; competitive repopulation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Genetic inactivation of Tet2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A different group from the conditional-knockout study above, but the same group as the 2009 human mutation survey in this collection, so that survey and this mouse model are one line of evidence rather than two.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A second group's mice also developed blood cancers after Tet2 was switched off.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[quivoron-2011] TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis (2011). https://pubmed.ncbi.nlm.nih.gov/21723201/ DOI: 10.1016/j.ccr.2011.06.003","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Myeloid and lymphoid compartments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"025d057c-7f15-5f97-b8c8-e536660c5682","evidence_kind":"source_excerpt","locator":"Lines 73-81","start_line":73,"end_line":81,"excerpt":"## tet2-inactivation-causes-mouse-malignancy\nInactivating Tet2 in mouse perturbed both early and late haematopoiesis in a cell-autonomous manner, gave the cells a competitive advantage, and eventually led to the development of haematological malignancies.\nModel/species: Tet2-inactivated mice; competitive repopulation\nOrganism: Mus musculus\nTissue/system: Myeloid and lymphoid compartments\nExposure: Genetic inactivation of Tet2\nDuration: In vivo, to malignancy\nLimits: A different group from the conditional-knockout study above, but the same group as the 2009 human mutation survey in this collection, so that survey and this mouse model are one line of evidence rather than two.\nPrimary reference: [quivoron-2011] TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis (2011). https://pubmed.ncbi.nlm.nih.gov/21723201/ DOI: 10.1016/j.ccr.2011.06.003","model_system":"Tet2-inactivated mice; competitive repopulation","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c0b9b176-985b-55c7-b8f5-f3ca16a7ddfe","stable_key":"import-a2968a2f-5b00-5212-8b8c-8a4262bcb149","title":"TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies located by Europe PMC title search, with every statement drafted from the retrieved abstract. Two pairs share a laboratory and are recorded as one line of evidence each. Genetic loss of function, pharmacological exposure and dietary depletion are kept as separate record types. Not publisher full text.","file_path":"","sha256":"22e2c8388d4f0c1813546ba6a9ccee3fa14c0c8f578bd9bd80103c1390b2536b","revision_id":"fbc29d8d-0420-562c-bfdb-1b5af42f2d08","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}